Skip to main content
SpringerLink
Log in

Serine Proteases

  • Reference work entry
  • First Online:
Handbook of Neurochemistry and Molecular Neurobiology

Abstract:

Serine proteases are an ancient and large group of proteolytic enzymes that utilize a uniquely activated serine residue to catalyze peptide bond hydrolysis. Members of this protease family are highly diversified and are involved in numerous physiological and pathological processes. Their enzymatic activities are tightly regulated through transcription, translation, zymogen activation, autolysis, and interaction with natural inhibitors. In this chapter, the authors will begin with a brief description of the structure and function of serine proteases. Next, several members of this family of enzymes, including thrombin, plasmin, plasminogen activators, kallikreins, and human trypsin 4 are presented. These sections will discuss the genomic localization, gene structure, and regulation of expression of these proteases followed by the description of their enzymatic specificity and biological functions focusing on processes in the central nervous system (CNS).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 299.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

5′-RACE:

rapid amplification of 5′-cDNA ends

AA:

amino acid

AD:

Alzheimer's disease

AP1:

activating protein 1

AP2:

activating protein 2

APP:

amyloid precursor protein

BPTI:

bovine pancreatic trypsin inhibitor

cAMP:

3′,5′-cyclic adenosine monophosphate

CNS:

central nervous system

CSF:

cerebrospinal fluid

EAE:

experimental autoimmune encephalomyelitis

ELISA:

enzyme-linked immunosorbent assay

EPO:

erythropoietin

FTD:

frontotemporal dementia

GDN:

glia-derived nexin

GFAP:

glial fibrillar acidic protein

GFP:

green fluorescent protein

GnRH:

gonadotropin-releasing hormone

GPCR:

G-protein coupled receptor

HBE:

human bronchial epithelial cell line

HEK:

human embryonic kidney cell line

HIF:

hypoxia-inducible factor

hK:

human kallikrein

hPSTI:

human pancreatic secretory inhibitor

HRE:

hypoxic response element

IGFBP-3:

insulin-like growth factor-binding protein-3

k cat :

catalytic constant

KLK:

kallikrein gene

K m :

Michaelis constant

LTP:

long-term potentiation

mAb:

monoclonal antibody

MALDI-MS:

matrix-assisted laser desorption ionization mass spectrometry

MBP:

myelin basic protein

MOG:

oligodendrocyte glycoprotein

MS:

multiple sclerosis

MSA:

multiple system atrophy

MSP:

myelencephalon specific protease

MUGB:

4-methylumbelliferyl 4-guanidinobenzoate

NF1:

nuclear factor 1

NMDA:

N-methyl-d-aspartate

PAI-1:

plasminogen activator inhibitor 1

PAR:

protease-activated receptor

PCR:

polymerase chain reaction

PD:

Parkinson's disease

PN1:

protease nexin I

PRSS:

serine protease gene

RT-PCR:

reverse transcription polymerase chain reaction

SP1:

signal protein 1

STI:

soybean trypsin inhibitor

TCR:

T-cell receptor

TGF-β:

transforming growth factor β

TM:

thrombomodulin

tPA:

tissue-type plasminogen activator

uPA:

urokinase-type plasminogen activator

uPAR:

urokinase-type plasminogen activator receptor

References

  • Akita H, Matsuyama T, Iso H, Sugita M, Yoshida S. 1997. Effects of oxidative stress on the expression of limbic-specific protease neuropsin and avoidance learning in mice. Brain Res 769: 86–96.

    Article  CAS  PubMed  Google Scholar 

  • Arai T, Miklóssy J, Klegeris A, Guo JP, McGeer PL. 2006 Thrombin and prothrombin are expressed by neurons and glial cells and accumulate in neurofibrillary tangles in Alzheimer disease brain. J Neuropathol Exp Neurol 65: 19–25.

    Article  CAS  PubMed  Google Scholar 

  • Asakai R, Davie EW, Chung DW. 1987. Organization of the gene for human factor XI. Biochemistry 26: 7221–7228.

    Article  CAS  PubMed  Google Scholar 

  • Baranes D, Lederfein D, Huang YY, Chen M, Bailey CH, Kandel ER. 1998 Tissue plasminogen activator contributes to the late phase of LTP and to synaptic growth in the hippocampal mossy fiber pathway. Neuron 21: 813–825.

    Article  CAS  PubMed  Google Scholar 

  • Barrett AJ, Rawlings ND. 1995. Families and clans of serine peptidases. Arch Biochem Biophys 318: 247–250.

    Article  CAS  PubMed  Google Scholar 

  • Barrett AJ, Rawlings ND, Woessner JF. (editors) 2004. Handbook of Proteolytic Enzymes. 2nd edition, Academic Press.

    Google Scholar 

  • Bender ML, Kézdy J. 1965. Mechanism of action of proteolytic enzymes. Annu Rev Biochem 34: 49–76.

    Article  CAS  PubMed  Google Scholar 

  • Bernett MJ, Blaber SI, Scarisbrick IA, Dhanarajan P, Thompson SM, et al. 2002. Crystal structure and biochemical characterization of human kallikrein 6 reveals that a trypsin-like kallikrein is expressed in the central nervous system. J Biol Chem 277: 24562–24570.

    Article  CAS  PubMed  Google Scholar 

  • Bhoola KD, Figueroa CD, Worthy K. 1992. Bioregulation of kinins: Kallikreins, kininogens, and kininases. Pharmacol Rev 44: 1–80.

    CAS  PubMed  Google Scholar 

  • Blaber SI, Ciric B, Christophi GP, Bernett MJ, Blaber M, et al. 2004. Targeting kallikrein 6 proteolysis attenuates CNS inflammatory disease. FASEB J 18: 920–922.

    CAS  PubMed  Google Scholar 

  • Blasi F, Carmeliet P. 2002. uPAR: A versatile signalling orchestrator. Nat Rev Mol Cell Biol 3: 932–943.

    Article  CAS  PubMed  Google Scholar 

  • Bode W, Mayr I, Baumann U, Huber R, Stone SR, et al. 1989. The refined 1.9-Ĺ crystal structure of human a-thrombin: Interaction with D-Phe-Pro-Arg chloromethylketone and significance of the Tyr-Pro-Pro-Trp insertion segment. EMBO J 8: 3467–3475.

    CAS  PubMed  Google Scholar 

  • Bode W, Turk D, Karshikov A. 1992. The refined 1.9-Ĺ X-ray crystal structure of D-Phe-Pro-Arg chloromethylketone-inhibited human a-thrombin: Structure analysis, overall structure, electrostatic properties, detailed active-site geometry, and structure-function relationships. Protein Sci 1: 426–471.

    Article  CAS  PubMed  Google Scholar 

  • Bode W, Schwager P, Huber R. 1978. The transition of bovine trypsinogen to a trypsin-like state upon strong ligand binding. The refined crystal structures of the bovine trypsinogen-pancreatic trypsin inhibitor complex and of its ternary complex with Ile–Val at 1.9 A resolution. J Mol Biol 118: 99–112.

    Article  CAS  PubMed  Google Scholar 

  • Bode W, Walter J, Huber R, Wenzel HR, Tschesche H. 1984. The refined 2.2-A (0.22-nm) X-ray crystal structure of the ternary complex formed by bovine trypsinogen, valine–valine and the Arg15 analogue of bovine pancreatic trypsin inhibitor. Eur J Biochem 144: 185–190.

    Article  CAS  PubMed  Google Scholar 

  • Borgono CA, Diamandis EP. 2004. The emerging roles of human tissue kallikreins in cancer. Nat Rev Cancer 4: 876–890.

    Article  CAS  PubMed  Google Scholar 

  • Borgono CA, Michael IP, Diamandis EP. 2004. Human tissue kallikreins: Physiologic roles and applications in cancer. Mol Cancer Res 2: 257–280.

    CAS  PubMed  Google Scholar 

  • Cavanaugh K, Gurwitz D, Cunningham DD, Bradshaw R. 1990. Reciprocal modulation of astrocyte stellation by thrombin and protease nexin-1. J Neurochem 54: 1735–1743.

    Article  CAS  PubMed  Google Scholar 

  • Chen ZL, Yoshida S, Kato K, Momota Y, Suzuki J, et al. 1995. Expression and activity-dependent changes of a novel limbic-serine protease gene in the hippocampus. J Neurosci 15: 5088–5097.

    CAS  PubMed  Google Scholar 

  • Christophi GP, Isackson PJ, Blaber S, Blaber M, Rodriguez M, et al. 2004. Distinct promoters regulate tissue-specific and differential expression of kallikrein 6 in CNS demyelinating disease. J Neurochem 91: 1439–1449.

    Article  CAS  PubMed  Google Scholar 

  • Citron BA, Smirnova IV, Arnold PM, Festoff BW. 2000. Upregulation of neurotoxic serine proteases, prothrombin, and protease-activated receptor 1 early after spinal cord injury. J Neurotrauma 17: 1191–1203.

    Article  CAS  PubMed  Google Scholar 

  • Citron BA, Smirnova IV, Zoubine MN, Festoff BW. 1997. Quantitative PCR analysis reveals novel expression of prothrombin mRNA and regulation of its levels in developing mouse muscle. Thromb Res 87: 303–313.

    Article  CAS  PubMed  Google Scholar 

  • Clements J. 1997. The molecular biology of the kallikreins and their roles in inflammation. In: Farmer S. (Ed.), The kinin system. Academic Press, New York, pp. 71–97.

    Chapter  Google Scholar 

  • Clements J, Hooper J, Dong Y, Harvey T. 2001. The expanded human kallikrein (KLK) gene family: Genomic organisation, tissue-specific expression and potential functions. Biol Chem 382: 5–14.

    Article  CAS  PubMed  Google Scholar 

  • Clements JA, Willemsen NM, Myers SA, Dong Y. 2004. The tissue kallikrein family of serine proteases: Functional roles in human disease and potential as clinical biomarkers. Crit Rev Clin Lab Sci 41: 265–312.

    Article  CAS  PubMed  Google Scholar 

  • Cleutjens KB, van Eekelen CC, Korput van der HA, Brinkmann AO, Trapman J. 1996. Two androgen response regions cooperate in steroid hormone regulated activity of the prostate-specific antigen promoter. J Biol Chem 271: 6379–6388.

    Article  CAS  PubMed  Google Scholar 

  • Cohen P, Graves HC, Peehl DM, Kamarei M, Giudice LC, et al. 1992. Prostate-specific antigen (PSA) is an insulin-like growth factor binding protein-3 protease found in seminal plasma. J Clin Endocrinol Metab 75: 1046–1053.

    Article  CAS  PubMed  Google Scholar 

  • Cottrell GS, Amadesi S, Grady EF, Bunnett NW. 2004. Trypsin IV, a novel agonist of protease-activated receptors 2 and 4. J Biol Chem 279: 13532–13539.

    Article  CAS  PubMed  Google Scholar 

  • Dano K, Andreasen PA, Grondahl-Hansen J, Kristensen P, Nielson LS, et al. 1985. Plasminogen activators, tissue degradation and cancer. Adv Cancer Res 44: 139–266.

    Article  CAS  PubMed  Google Scholar 

  • Davie EW, Fujikawa K, Kisiel W. 1991. The coagulation cascade: Initiation, maintenance, and regulation. Biochemistry 30: 10363–10370.

    Article  CAS  PubMed  Google Scholar 

  • Davies BJ, Pickard BS, Steel M, Morris RG, Lathe R. 1998. Serine proteases in rodent hippocampus. J Biol Chem 273: 23004–23011.

    Article  CAS  PubMed  Google Scholar 

  • Debeir T, Gueugnon J, Vige X, Benavides J. 1996. Transduction mechanisms involved in thrombin receptor-induced nerve growth factor secretion and cell division in primary cultures of astrocytes. J Neurochem 66: 2320–2328.

    Article  CAS  PubMed  Google Scholar 

  • Degen SJ, Heckel JL, Reich E, Degen JL. 1987. The murine urokinase-type plasminogen activator gene. Biochemistry 26: 8270–8279.

    Article  CAS  PubMed  Google Scholar 

  • Degen SJ, MacGillivray RT, Davie, E.W. 1983. Characterization of the complementary deoxyribonucleic acid and gene coding for human prothrombin. Biochemistry 22: 2087–2097.

    Article  CAS  PubMed  Google Scholar 

  • DeLano WL. 2002 PyMOL Molecular Graphics System, DeLano Scientific, San Carlos, CA, USA.

    Google Scholar 

  • Deschepper CF, Bigorma V, Berens ME, Lapointe MC. 1991. Production of thrombin and antithrombin III by brain and astroglial cell cultures. Mol Brain Res 11: 355–358.

    Article  CAS  PubMed  Google Scholar 

  • Diamandis EP, Okui A, Mitsui S, Luo LY, Soosaipillai A, et al. 2002. Human kallikrein 11: A new biomarker of prostate and ovarian carcinoma. Cancer Res 62: 295–300.

    CAS  PubMed  Google Scholar 

  • Diamandis EP, Scorilas A, Kishi T, Blennow K, Luo LY, et al. 2004. Altered kallikrein 7 and 10 concentrations in cerebrospinal fluid of patients with Alzheimer's disease and frontotemporal dementia. Clin Biochem 37: 230–237.

    Article  CAS  PubMed  Google Scholar 

  • Diamandis EP, Yousef GM. 2002. Human tissue kallikreins: A family of new cancer biomarkers. Clin Chem 48: 1198–1205.

    CAS  PubMed  Google Scholar 

  • Diamandis EP, Yousef GM, Clements J, Ashworth LK, Yoshida S, et al. 2000a. New nomenclature for the human tissue kallikrein gene family. Clin Chem 46: 1855–1858.

    CAS  Google Scholar 

  • Diamandis EP, Yousef GM, Petraki C, Soosaipillai AR. 2000b. Human kallikrein 6 as a biomarker of Alzheimer's disease. Clin Biochem 33: 663–667.

    Article  CAS  Google Scholar 

  • Diamandis EP, Yousef GM, Soosaipillai AR, Bunting P. 2000c. Human kallikrein 6 (zyme/protease M/neurosin): A new serum biomarker of ovarian carcinoma. Clin Biochem 33: 579–583.

    Article  CAS  Google Scholar 

  • Diamandis EP, Yousef GM, Soosaipillai AR, Grass L, Porter A, et al. 2000d. Immunofluorometric assay of human kallikrein 6 (zyme/protease M/neurosin) and preliminary clinical applications. Clin Biochem 33: 369–375.

    Article  CAS  Google Scholar 

  • Diederichs S, Bulk E, Steffen B, Ji P, Tickenbrock L, et al. 2004. S100 family members and trypsinogens are predictors of distant metastasis and survival in early-stage non-small cell lung cancer. Cancer Res 64 (16): 5564–5569.

    Article  CAS  PubMed  Google Scholar 

  • Dihanich M, Kaser M, Reinhard E, Cunningham D, Monard D. 1991. Prothrombin mRNA is expressed by cells of the nervous system. Neuron Acta Anat 6: 575–581.

    CAS  Google Scholar 

  • Dihanich M, Spiess M. 1994. A novel serine proteinase-like sequence from human brain. Biochim Biophys Acta 1218: 225–228.

    CAS  PubMed  Google Scholar 

  • Dong Y, Kaushal A, Bui L, Chu S, Fuller PJ, et al. 2001. Human kallikrein 4 (KLK4) is highly expressed in serous ovarian carcinomas. Clin Cancer Res 7: 2363–2371.

    CAS  PubMed  Google Scholar 

  • Donovan FM, Pike CJ, Cotman CW, Cunningham DD. 1997. Thrombin induces apoptosis in cultured neurons and astrocytes via a pathway requiring tyrosine kinase and RhoA activities. J Neurosci 17: 5316–5326.

    CAS  PubMed  Google Scholar 

  • Drapkin PT, Monard D, Silverman AJ. 2002. The role of serine proteases and serine protease inhibitors in the migration of gonadotropin-releasing hormone neurons. BMC Dev Biol 2: 1

    Article  PubMed  Google Scholar 

  • Ekholm E, Egelrud T. 1999. Stratum corneum chymotryptic enzyme in psoriasis. Arch Dermatol Res 291: 195–200.

    Article  CAS  PubMed  Google Scholar 

  • Emi M, Nakamura Y, Ogawa M, Yamamoto T, Nishide T, et al. 1986. Cloning, characterization, and nucleotide sequences of two cDNAs encoding human pancreatic trypsinogens. Gene 41: 305–310.

    Article  CAS  PubMed  Google Scholar 

  • Fehlhammer H, Bode W, Huber R. 1977. Crystal structure of bovine trypsinogen at 1–8 A resolution. II. Crystallographic refinement, refined crystal structure and comparison with bovine trypsin. J Mol Biol 111: 415–438.

    Article  CAS  PubMed  Google Scholar 

  • Feng P, Ohlsson M, Ny T. 1990. The structure of the TATA-less rat tissue-type plasminogen activator gene. Species-specific sequence divergences in the promoter predict differences in regulation of gene expression. J Biol Chem 265: 2022–2027.

    CAS  PubMed  Google Scholar 

  • Festoff BW, Suo Z, Citron BA. 2001. Plasticity and stabilization of neuromuscular and CNS synapses: Interactions between thrombin protease signaling pathways and tissue transglutaminase. Int Rev Cytol 211: 153–177.

    Article  CAS  PubMed  Google Scholar 

  • Festoff BW. 2004. Role of proteinase activated receptors in brain function. In: Proteases in Biology and Diseases, Proteases in the Brain. Lendeckel U, Hooper NM, editors. Chapter 13, Springer science + Business Media Inc, New York, 3: 330.

    Google Scholar 

  • Figueroa BE, Keep RF, Betz AL, Hoff JT. 1998. Plasminogen activators potentiate thrombin-induced brain injury. Stroke 29: 1202–1207.

    CAS  PubMed  Google Scholar 

  • Frenette G, Tremblay RR, Lazure C, Dube JY. 1997. Prostatic kallikrein hK2, but not prostate-specific antigen (hK3), activates single-chain urokinase-type plasminogen activator. Int J Cancer 71: 897–899.

    Article  CAS  PubMed  Google Scholar 

  • Gan L, Lee I, Smith R, Argonza-Barrett R, Lei H, et al. 2000. Sequencing and expression analysis of the serine protease gene cluster located in chromosome 19q13 region. Gene 257: 119–130.

    Article  CAS  PubMed  Google Scholar 

  • Garcia-Rocha M, Avila J, Armas-Portela R. 1994. Tissue-type plasminogen activator (tPA) is the main plasminogen activator associated with isolated rat nerve growth cones. Neurosci Lett 180: 123–126.

    Article  CAS  PubMed  Google Scholar 

  • Gingrich MB, Traynelis SF. 2000. Serine proteases and brain damage – is there a link? Trends Neurosci 23: 399–407.

    Article  CAS  PubMed  Google Scholar 

  • Gingrich MB, Junge CE, Lyuboslavsky P, Traynelis SF. 2000. Potentiation of NMDA receptor function by the serine protease thrombin. J Neurosci. 20: 4582–4595.

    CAS  PubMed  Google Scholar 

  • Gomis-Ruth FX, Bayes A, Sotiropoulou G, Pampalakis G, Tsetsenis T, et al. 2002a. The structure of human prokallikrein 6 reveals a novel activation mechanism for the kallikrein family. J Biol Chem 277: 27273–27281.

    Article  CAS  Google Scholar 

  • Grabham P, Cunningham, DD. 1995. Thrombin receptor activation stimulates astrocyte proliferation and reversal of stellation by distinct pathways: involvement of tyrosine phosphorylation. J Neurochem 64: 583–591.

    Article  CAS  PubMed  Google Scholar 

  • Gráf L. 1995. The structural basis of serine protease action: The fourth dimension. In: Zwilling, R. (Ed.), Natural Sciences and Human Thought. Springer-Verlag, Heidelberg, pp. 139–148.

    Google Scholar 

  • Grishina Z, Ostrowska E, Halangk W, Sahin-Toth M, Reiser G. 2005. Activity of recombinant trypsin isoforms on human proteinase-activated receptors (PAR): Mesotrypsin cannot activate epithelial PAR-1, -2, but weakly activates brain PAR-1. Br J Pharmacol 146: 990–999.

    Article  CAS  PubMed  Google Scholar 

  • Hardy J, Selkoe DJ. 2002. The amyloid hypothesis of Alzheimer's disease: Progress and problems on the road to therapeutics. Science 297, 353–356.

    Article  CAS  PubMed  Google Scholar 

  • Harvey TJ, Hooper JD, Myers SA, Stephenson SA, Ashworth LK, et al. 2000. Tissue-specific expression patterns and fine mapping of the human kallikrein (KLK) locus on proximal 19q13.4. J Biol Chem 275: 37397–37406.

    Article  CAS  PubMed  Google Scholar 

  • Hedstrom, L, Lin TY, Fast W. 1996. Hydrophobic interactions control zymogen activation in the trypsin family of serine proteases. Biochemistry 35: 4515–4523.

    Article  CAS  PubMed  Google Scholar 

  • Heidtmann HH, Nettelbeck DM, Mingels A, Jager R, Welker HG, et al. 1999. Generation of angiostatin-like fragments from plasminogen by prostate-specific antigen. Br J Cancer 81: 1269–1273.

    Article  CAS  PubMed  Google Scholar 

  • Henderson R, 1970. Structure of crystalline α-chymotrypsin. IV. The structure of indoleacryloyl-α-chyotrypsin and its relevance to the hydrolytic mechanism of the enzyme. J Mol Biol 54: 341–354.

    Article  CAS  PubMed  Google Scholar 

  • Higgins DL, Lewis SD, Shafer JA. 1983. Steady state kinetic parameters for the thrombin-catalyzed conversion of human fibrinogen to fibrin. J Biol Chem 258: 9276–9282.

    CAS  PubMed  Google Scholar 

  • Hirata A, Yoshida S, Inoue N, Matsumoto-Miyai K, Ninomiya A et al. 2001. Abnormalities of synapses and neurons in the hippocampus of neuropsin-deficient mice. Mol Cell Neurosci 17: 600–610.

    Article  CAS  PubMed  Google Scholar 

  • Hollenberg MD, Saifeddine M, al-Ani B, Kawabata, A. 1997. Proteinase-activated receptors: Structural requirements for activity, receptor cross-reactivity, and receptor selectivity of receptor-activating peptides. Can J Physiol Pharmacol 75: 832–841.

    Article  CAS  PubMed  Google Scholar 

  • Hood L, Rowen L, Koop BF. 1995. Human and mouse T-cell receptor loci: Genomics, evolution, diversity, and serendipity. Ann N Y Acad Sci 758: 390–412.

    Article  CAS  PubMed  Google Scholar 

  • Ho GJ, Smirnova IV, Akaaboune M, Hantai D, Festoff BW. 1994. Serine proteases and their serpin inhibitors in Alzheimer's disease. Biomed Pharmacother 48: 296–304.

    Article  CAS  PubMed  Google Scholar 

  • Hoyer-Hansen G, Rřnne E, Solberg H, Behrendt N, Ploug M, et al. 1992. Urokinase plasminogen activator cleaves its cell surface receptor releasing the ligand-binding domain. J Biol Chem 267: 18224–18229.

    CAS  PubMed  Google Scholar 

  • Huang YY, Bach ME, Lipp HP, Zhuo M, Wolfer DP, et al. 1996. Mice lacking the gene encoding tissue-type plasminogen activator show a selective interference with late-phase long-term potentiation in both Schaffer collateral and mossy fiber pathways. Proc Natl Acad Sci USA 6;93: 8699–8704.

    Article  Google Scholar 

  • Huber R, Bode W. 1978. Structural basis of the activation and action of trypsin. Acc Chem Res 11: 114–122.

    Article  CAS  Google Scholar 

  • Ishihara H, Connolly AJ, Zeng D, Kahn ML, Zheng YW, et al. 1997. Protease-activated receptor 3 is a second thrombin receptor in humans. Nature 386: 502–506.

    Article  CAS  PubMed  Google Scholar 

  • Iwata A, Maruyama M, Akagi T, Hashikawa T, Kanazawa I, et al. 2003. α-Synuclein degradation by serine protease neurosin: Implication for pathogenesis of synucleinopathies. Hum Mol Genet 12: 2625–2635.

    Article  CAS  PubMed  Google Scholar 

  • Jaffa AA, Chai KX, Chao J, Chao L, Mayfield R K. 1992. Effects of diabetes and insulin on expression of kallikrein and renin genes in the kidney. Kidney Int 41: 789–795.

    Article  CAS  PubMed  Google Scholar 

  • Kahn ML, Hammes SR, Botka C, Coughlin SR. 1998. Gene and locus structure and chromosomal localization of the protease-activated receptor gene family. J Biol Chem 273: 23290–23296.

    Article  CAS  PubMed  Google Scholar 

  • Katona G, Berglund GI, Hajdu J, Gráf L, Szilágyi L. 2002. Crystal structure reveals basis for the inhibitor resistance of human brain trypsin. J Mol Biol 315: 1209–1218.

    Article  CAS  PubMed  Google Scholar 

  • Katz BA, Liu B, Barnes M, Springman EB. 1998a. Crystal structure of recombinant human tissue kallikrein at 2.0 A resolution. Protein Sci 7: 875–885.

    Article  CAS  Google Scholar 

  • Kauffman DL. 1965. The disulfide bridges of trypsin. J Mol Biol 12: 929–932.

    Article  CAS  PubMed  Google Scholar 

  • Killian CS, Corral DA, Kawinski E, Constantine RI. 1993. Mitogenic response of osteoblast cells to prostate-specific antigen suggests an activation of latent TGF-β and a proteolytic modulation of cell adhesion receptors. Biochem Biophys Res Commun 192: 940–947.

    Article  CAS  PubMed  Google Scholar 

  • Kim H, Scorilas A, Katsaros D, Yousef GM, Massobrio M, et al. 2001. Human kallikrein gene 5 (KLK5) expression is an indicator of poor prognosis in ovarian cancer. Br J Cancer 84: 643–650.

    Article  CAS  PubMed  Google Scholar 

  • Koh PO, Kang BI, Kim GS, Oh YS, Won CK. 2005. The effect of thrombin on astrocyte stellation with regional specificity. J Vet Med Sci 67: 1047–1050.

    Article  CAS  PubMed  Google Scholar 

  • Komai S, Matsuyama T, Matsumoto K, Kato K, Kobayashi M, et al. 2000. Neuropsin regulates an early phase of schaffer-collateral long-term potentiation in the murine hippocampus. Eur J Neurosci 12: 1479–1486.

    Article  CAS  PubMed  Google Scholar 

  • Kooistra T, Bosma PJ, Toet K, Cohen CH, Griffioen M, et al. 1991. Role of protein kinase C and cyclic adenosine monophosphate in the regulation of tissue-type plasminogen activator, plasminogen activator inhibitor-1, and platelet-derived growth factor mRNA levels in human endothelial cells. Possible involvement of proto-oncogenes c-jun and c-fos. Arterioscler Thromb 11: 1042–1052.

    CAS  PubMed  Google Scholar 

  • Kossiakoff AA, Spencer SA. 1981. Direct determination of the protonation states of aspartic acid-102 and histidine-57 in the tetrahedral intermediate of serine proteinases: Neutron structure of trypsin. Biochemistry 20: 6462–6474 .

    Article  CAS  PubMed  Google Scholar 

  • Kraut J. 1971. Chymotrypsinogen: X-ray structure. In: The Enzymes, Vol. 3. Boyer PD, editor. New York: Academic Press; pp. 165–183.

    Google Scholar 

  • Krishnaswamy S, Nesheim ME, Pryzdial EL, Mann KG. 1993. Assembly of prothrombinase complex. Methods Enzymol 222: 260–280.

    Article  CAS  PubMed  Google Scholar 

  • Kuliopulos A, Covic L, Seeley SK, Sheridan PJ, Helin J, et al. 1999. Plasmin desensitization of the PAR1 thrombin receptor: Kinetics, sites of truncation, and implications for thrombolytic therapy. Biochemistry 38: 4572–4585.

    Article  CAS  PubMed  Google Scholar 

  • Kurlender L, Borgono C, Michael IP, Obiezu C, Elliott MB, et al. 2005. A survey of alternative transcripts of human tissue kallikrein genes. Biochim Biophys Acta 1755: 1–14.

    CAS  PubMed  Google Scholar 

  • Laxmikanthan G, Blaber SI, Bernett MJ, Scarisbrick IA, Juliano MA, et al. 2005. 1.70 A X-ray structure of human apo kallikrein 1: Structural changes upon peptide inhibitor/substrate binding. Proteins 58: 802–814.

    Article  CAS  PubMed  Google Scholar 

  • Lee KR, Drury I, Vitarbo E, Hoff JT. 1997. Seizures induced by intracerebral injection of thrombin: A model of intracerebral hemorrhage. J Neurosurg 87: 73–78.

    Article  CAS  PubMed  Google Scholar 

  • Lee KR, Colon GP, Betz AL, Keep RF, Kim S, et al. 1996. Edema from intracerebral hemorrhage: The role of thrombin. J Neurosurg 84: 91–96.

    Article  CAS  PubMed  Google Scholar 

  • Lesk AM, Fordham WD. 1996 Conservation and variability in the structures of serine proteinases of the chymotrypsin family. J Mol Biol 258: 501–537.

    Article  CAS  PubMed  Google Scholar 

  • Lijnen HR, Collen D. 1991. Strategies for the improvement of thrombolytic agents. Thromb Haemost 66: 88–110.

    CAS  PubMed  Google Scholar 

  • Lijnen HR, Bachmann F, Collen D, Ellis V, Pannekoek H, et al. 1994. Mechanisms of plasminogen activation. J Intern Med 236: 415–424.

    Article  CAS  PubMed  Google Scholar 

  • Lilja H. 1985. A kallikrein-like serine protease in prostatic fluid cleaves the predominant seminal vesicle protein. J Clin Invest 76: 1899–1903.

    Article  CAS  PubMed  Google Scholar 

  • Little SP, Dixon EP, Norris F, Buckley W, Becker GW, et al. 1997. Zyme, a novel and potentially amyloidogenic enzyme cDNA isolated from Alzheimer's disease brain. J Biol Chem 272: 25135–25142.

    Article  CAS  PubMed  Google Scholar 

  • Lorand L, Jeong JM, Radek JT, Wilson J. 1993. Human plasma factor XIII: Subunit interactions and activation of zymogen. Methods Enzymol 222: 22–35.

    Article  CAS  PubMed  Google Scholar 

  • Ludwig M, Wohn KD, Schleuning WD, Olek K. 1992. Allelic dimorphism in the human tissue-type plasminogen activator (tPA) gene as a result of an Alu insertion/deletion event. Hum Genet 88: 388–392.

    Article  CAS  PubMed  Google Scholar 

  • Luo LY, Bunting P, Scorilas A, Diamandis EP. 2001a. Human kallikrein 10: A novel tumor marker for ovarian carcinoma?. Clin Chim Acta 306: 111–118.

    Article  CAS  Google Scholar 

  • Luo LY, Katsaros D, Scorilas A, Fracchioli S, Piccinno R, et al. 2001b. Prognostic value of human kallikrein 10 expression in epithelial ovarian carcinoma. Clin Cancer Res 7: 2372–2379.

    CAS  Google Scholar 

  • Luthi A, Van der Putten H, Botteri FM, Mansuy IM, Meins M, et al. 1997. Endogenous serine protease inhibitor modulates epileptic activity and hippocampal long-term potentiation. J Neurosci 17: 4688–4699.

    CAS  PubMed  Google Scholar 

  • Macfarlane SR, Seatter MJ, Kanke T, Hunter GD, Plevin R. 2001. Proteinase-activated receptors 4. Pharmacol Rev 53: 245–282.

    CAS  PubMed  Google Scholar 

  • Magklara A, Mellati AA, Wasney GA, Little SP, Sotiropoulou G, et al. 2003. Characterization of the enzymatic activity of human kallikrein 6: Autoactivation, substrate specificity, and regulation by inhibitors. Biochem Biophys Res Commun 307: 948–955.

    Article  CAS  PubMed  Google Scholar 

  • Mann KG. 1994 Prothrombin and thrombin 1–184–199, Philadelphia: Lippincott Company.

    Google Scholar 

  • Marcondes S, Antunes E. 2005. The plasma and tissue kininogen-kallikrein-kinin system: Role in the cardiovascular system. Curr Med Chem Cardiovasc Hematol Agents 3: 33–44.

    Article  CAS  PubMed  Google Scholar 

  • Margolius HS, Horwitz D, Pisano JJ, Keiser HR. 1974. Urinary kallikrein excretion in hypertensive man. Relationships to sodium intake and sodium-retaining steroids. Circ Res 35: 820–825.

    CAS  PubMed  Google Scholar 

  • Maroteaux L, Campanelli JT, Scheller RH. 1988. Synuclein: A neuron-specific protein localized to the nucleus and presynaptic nerve terminal. J Neurosci 8: 2804–2815.

    CAS  PubMed  Google Scholar 

  • Marsit CJ, Okpukpara C, Danaee H, Kelsey KT. 2005. Epigenetic silencing of the PRSS3 putative tumor suppressor gene in non-small cell lung cancer 1. Mol Carcinog 44: 146–150.

    Article  CAS  PubMed  Google Scholar 

  • Mason AJ, Evans BA, Cox DR, Shine J, Richards RI. 1983. Structure of mouse kallikrein gene family suggests a role in specific processing of biologically active peptides. Nature 303: 300–307.

    Article  CAS  PubMed  Google Scholar 

  • Matsui H, Kimura A, Yamashiki N, Moriyama A, Kaya M, et al. 2000. Molecular and biochemical characterization of a serine proteinase predominantly expressed in the medulla oblongata and cerebellar white matter of mouse brain. J Biol Chem 275: 11050–11057.

    Article  CAS  PubMed  Google Scholar 

  • Matsumoto-Miyai K, Ninomiya A, Yamasaki H, Tamura H, Nakamura Y, et al. 2003. NMDA-dependent proteolysis of presynaptic adhesion molecule L1 in the hippocampus by neuropsin. J Neurosci 23: 7727–7736.

    CAS  PubMed  Google Scholar 

  • Medcalf RL, Ruegg M, Schleuning WD. 1990. A DNA motif related to the cAMP-responsive element and an exon-located activator protein-2 binding site in the human tissue-type plasminogen activator gene promoter cooperate in basal expression and convey activation by phorbol ester and cAMP. J Biol Chem 265: 14618–14626.

    CAS  PubMed  Google Scholar 

  • Medveczky P, Antal J, Patthy A, Kékesi K, Juhász G, et al. 2006. Myelin basic protein, an autoantigen in multiple sclerosis, is selectively processed by human trypsin 4. FEBS Lett 580: 545–552.

    Article  CAS  PubMed  Google Scholar 

  • Meier N, Dear TN, Boehm T. 1999. A novel serine protease overexpressed in the hair follicles of nude mice. Biochem Biophys Res Commun 258: 374–378.

    Article  CAS  PubMed  Google Scholar 

  • Melegos DN, Freedman MS, Diamandis EP. 1997. Prostate-specific antigen in cerebrospinal fluid. Clin Chem 43: 855.

    CAS  PubMed  Google Scholar 

  • Minn A, Schubert M, Neiss WF, Muller-Hill B. 1998. Enhanced GFAP expression in astrocytes of transgenic mice expressing the human brain-specific trypsinogen IV 24. Glia 22: 338–347.

    Article  CAS  PubMed  Google Scholar 

  • Mitsui S, Tsuruoka N, Yamashiro K, Nakazato H, Yamaguchi N. 1999. A novel form of human neuropsin, a brain-related serine protease, is generated by alternative splicing and is expressed preferentially in human adult brain. Eur J Biochem 260: 627–634.

    Article  CAS  PubMed  Google Scholar 

  • Mitsui S, Yamada T, Okui A, Kominami K, Uemura H, et al. 2000. A novel isoform of a kallikrein-like protease, TLSP/hippostasin, (PRSS20), is expressed in the human brain and prostate. Biochem Biophys Res Commun 272: 205–211.

    Article  CAS  PubMed  Google Scholar 

  • Mohanam S, Chandrasekar N, Yanamandra N, Khawar S, Mirza F, et al. 2002. Modulation of invasive properties of human glioblastoma cells stably expressing amino-terminal fragment of urokinase-type plasminogen activator. Oncogene. 21: 7824–7830.

    Article  CAS  PubMed  Google Scholar 

  • Mohanam S, Gladson CL, Rao CN, Rao JS. 1999. Biological significance of the expression of urokinase-type plasminogen activator receptors (uPARs) in brain tumors. Front Biosci 4: D178–187.

    Article  CAS  PubMed  Google Scholar 

  • Momota Y, Yoshida S, Ito J, Shibata M, Kato K, et al. 1998. Blockade of neuropsin, a serine protease, ameliorates kindling epilepsy. Eur J Neurosci 10: 760–764.

    Article  CAS  PubMed  Google Scholar 

  • Movat HZ. 1979. Bradykinin, kallidin and kallikrein. In: The plasma kallikrein–kinin system and its interrelationship with other components of the blood. Erdos EG, editor. Berlin: Springer-Verlag; pp. 1–89.

    Google Scholar 

  • Nelson RB, Siman R. 1990. Thrombin and its inhibitors regulate morphological and biochemical differentiation of astrocytes in vitro. Dev Brain Res 54: 93–104.

    Article  CAS  Google Scholar 

  • Nelson PS, Gan L, Ferguson C, Moss P, Gelinas R, et al. 1999. Molecular cloning and characterization of prostase, an androgen-regulated serine protease with prostate-restricted expression. Proc Natl Acad Sci USA 96: 3114–3119.

    Article  CAS  PubMed  Google Scholar 

  • Németh AL, Medveczky P, Tóth J, Siklódi E, Schlett K, Patthy A, Palkovits M, Ovádi J, Tőkési N, Németh P, Szilágyi L, Gráf L. 2006. Unconventional translation initiation of trypsinogen 4 at a CUG codon with an N-terminal leucine: a possible means to regulate gene exxpression. (under revision in FEBS J)

    Google Scholar 

  • Niclou SP, Suidan HS, Pavlik A, Vejsada R, Monard D. 1998. Changes in the expression of proteaseactivated receptor 1 and protease nexin-1 mRNA during rat nervous system development and after nerve lesion. Eur J Neurosci 10: 1590–1607.

    Article  CAS  PubMed  Google Scholar 

  • Nicole O, Ali C, Docagne F, Plawinski L, Mac Kenzie ET, et al. 2001. Neuroprotection mediated by glial cell line-derived neurotrophic factor: Involvement of a reduction of NMDA-induced calcium influx by the mitogen-activated protein kinase pathway. J Neurosci 21: 3024–3033.

    CAS  PubMed  Google Scholar 

  • Nyaruhucha CN, Kito M, Fukuoka SI. 1997. Identification and expression of the cDNA-encoding human mesotrypsin(ogen), an isoform of trypsin with inhibitor resistance. J Biol Chem 272: 10573–10578.

    Article  CAS  PubMed  Google Scholar 

  • Obiezu CV, Diamandis EP. 2005. Human tissue kallikrein gene family: Applications in cancer. Cancer Lett 224: 1–22.

    CAS  PubMed  Google Scholar 

  • Obiezu CV, Scorilas A, Katsaros D, Massobrio M, Yousef GM, et al. 2001. Higher human kallikrein gene 4 (KLK4) expression indicates poor prognosis of ovarian cancer patients. Clin Cancer Res 7: 2380–2386.

    CAS  PubMed  Google Scholar 

  • Ogawa K, Yamada T, Tsujioka Y, Taguchi J, Takahashi M, et al. 2000. Localization of a novel type trypsin-like serine protease, neurosin, in brain tissues of Alzheimer's disease and Parkinson's disease. Psychiatry Clin Neurosci 54: 419–426.

    Article  CAS  PubMed  Google Scholar 

  • Oka T, Akisada M, Okabe A, Sakurai K, Shiosaka S, et al. 2002. Extracellular serine protease neuropsin (KLK8) modulates neurite outgrowth and fasciculation of mouse hippocampal neurons in culture. Neurosci Lett 321: 141–144.

    Article  CAS  PubMed  Google Scholar 

  • Okabe A, Momota Y, Yoshida S, Hirata A, Ito J, et al. 1996. Kindling induces neuropsin mRNA in the mouse brain. Brain Res 728: 116–120.

    Article  CAS  PubMed  Google Scholar 

  • Okui A, Kominami K, Uemura H, Mitsui S, Yamaguchi N. 2001. Characterization of a brain-related serine protease, neurosin (human kallikrein 6), in human cerebrospinal fluid. Neuroreport 12: 1345–1350.

    Article  CAS  PubMed  Google Scholar 

  • O'Rourke JF, Dachs GU, Gleadle JM, Maxwell PH, Pugh CW, et al. 1997. Hypoxia response elements. Oncol Res 9: 327–332.

    PubMed  Google Scholar 

  • Ossovskaya VS, Bunnett NW. 2004. Protease-activated receptors: Contribution to physiology and disease. Physiol Rev 84: 579–621.

    Article  CAS  PubMed  Google Scholar 

  • Page EL, Robitaille GA, Pouyssegur J, Richard DE. 2002. Induction of hypoxia-inducible factor-1α by transcriptional and translational mechanisms. J Biol Chem 277: 48403–48409.

    Article  CAS  PubMed  Google Scholar 

  • Patthy L. 1990. Evolutionary assembly of blood coagulation proteins. Semin Thromb Hemost 16: 245–259.

    Article  CAS  PubMed  Google Scholar 

  • Pawlak R, Magarinos AM, Melchor J, McEwen B, Strickland S. 2003. Tissue plasminogen activator in the amygdala is critical for stress-induced anxiety-like behavior. Nat Neurosci 6: 168–174.

    Article  CAS  PubMed  Google Scholar 

  • Petraki CD, Karavana VN, Skoufogiannis PT, Little SP, Howarth DJ, et al. 2001. The spectrum of human kallikrein 6 (zyme/protease M/neurosin) expression in human tissues as assessed by immunohistochemistry. J Histochem Cytochem 49: 1431–1441.

    CAS  PubMed  Google Scholar 

  • Pindon A, Berry M, Hantai D. 2000. Thrombomodulin as a new marker of lesion-induced astrogliosis: Involvement of thrombin through the G-protein-coupled protease-activated receptor-1. J Neurosci 20: 2543–2550.

    CAS  PubMed  Google Scholar 

  • Pindon A, Hantai D, Jandrot-Perrus M, Festoff BW. 1997. Novel expression and localization of active thrombomodulin on the surface of mouse brain astrocytes. Glia 19: 259–68.

    Article  CAS  PubMed  Google Scholar 

  • Polgár L, Bender ML. 1969. The nature of general base-general acid catalysis in serine proteases. Proc Natl Acad Sci USA 64: 1335–1342.

    Article  PubMed  Google Scholar 

  • Rao JS, Baker JB, Morantz RA, Kimler B, Evans R, Festoff BW. 1990. Serpin inhibitors of urokinase and thrombin in normal rat brain and the 9L brain tumor: evidence for elevated expression of protease nexin I-like inhibitor and a novel sodium dodecyl sulfate-activated tumor antithrombin. Cancer Res 50: 5039–5044.

    CAS  PubMed  Google Scholar 

  • Rawlings ND, Barrett AJ. 1993. Evolutionary families of peptidases. Biochem J 290 (Pt 1): 205–218.

    CAS  PubMed  Google Scholar 

  • Resnati M, Pallavicini I, Wang JM, Oppenheim J, Serhan CN, et al. The fibrinolytic receptor for urokinase activates the G protein-coupled chemotactic receptor FPRL1/LXA4R. Proc Natl Acad Sci USA 99: 1359–1364.

    Google Scholar 

  • Rinderknecht H, Renner IG, Abramson SB, Carmack C. 1984. Mesotrypsin: A new inhibitor-resistant protease from a zymogen in human pancreatic tissue and fluid. Gastroenterology 86: 681–692.

    CAS  PubMed  Google Scholar 

  • Rittenhouse HG, Finlay JA, Mikolajczyk SD, Partin AW. 1998. Human Kallikrein 2 (hK2) and prostate-specific antigen (PSA): Two closely related, but distinct, kallikreins in the prostate. Crit Rev Clin Lab Sci. 35: 275–368.

    Article  CAS  PubMed  Google Scholar 

  • Robertus JD, Kraut J, Alden RA, Birktoft JJ. 1972. Subtilisin; a stereochemical mechanism involving transition-state stabilization. Biochemistry 11: 4293–4303.

    Article  CAS  PubMed  Google Scholar 

  • Rohatgi T, Sedehizade F, Reymann KG, Reiser, G. 2004. Protease-activated receptors in neuronal development, neurodegeneration, and neuroprotection: Thrombin as signaling molecule in the brain. Neuroscientist 10: 501–512.

    Article  CAS  PubMed  Google Scholar 

  • Rowen L, Koop BF, Hood L. 1996. The complete 685-kilobase DNA sequence of the human β T cell receptor locus 35. Science 272: 1755–1762.

    Article  CAS  PubMed  Google Scholar 

  • Rowen L, Williams E, Glusman G, Linardopoulou E, Friedman C, et al. 2005. Interchromosomal segmental duplications explain the unusual structure of PRSS3, the gene for an inhibitor-resistant trypsinogen. Mol Biol Evol 22: 1712–1720.

    Article  CAS  PubMed  Google Scholar 

  • Royle NJ. 1987. Human gene encoding prothrombin and ceruloplasmin map to 11p11-q12 and 3q21–24, respectively. Somat Cell Mol Genet 13: 285–292.

    Article  CAS  PubMed  Google Scholar 

  • Salles FJ, Strickland S. 2002. Localization and regulation of the tissue plasminogen activator-plasmin system in the hippocampus. J Neurosci 22: 2125–2134.

    CAS  PubMed  Google Scholar 

  • Sappino AP, Madani R, Huarte J, Belin D, Kiss JZ, et al. 1993. Extracellular proteolysis in the adult murine brain. J Clin Invest 92: 679–685.

    Article  CAS  PubMed  Google Scholar 

  • Scarisbrick IA, Blaber SI, Lucchinetti CF, Genain CP, Blaber M, et al. 2002. Activity of a newly identified serine protease in CNS demyelination. Brain 125: 1283–1296.

    Article  CAS  PubMed  Google Scholar 

  • Scarisbrick IA, Isackson PJ, Ciric B, Windebank AJ, Rodriguez M. 2001. MSP, a trypsin-like serine protease, is abundantly expressed in the human nervous system. J Comp Neurol 431: 347–361.

    Article  CAS  PubMed  Google Scholar 

  • Scarisbrick IA, Towner MD, Isackson PJ. 1997. Nervous system-specific expression of a novel serine protease: Regulation in the adult rat spinal cord by excitotoxic injury. J Neurosci 17: 8156–8168.

    CAS  PubMed  Google Scholar 

  • Schachter, M. 1979. Kallikreins (kininogenases) - a group of serine proteases with bioregulatory actions. Pharmacol Rev 31: 1–17.

    CAS  PubMed  Google Scholar 

  • Schechter I, Berger A. 1967. On the size of the active site in proteases. I. Papain. Biochem Biophys Res Commun 27: 157–162.

    Article  CAS  PubMed  Google Scholar 

  • Schmidt AE, Ogawa T, Gailani D, Bajaj SP. 2004. Structural role of Gly(193) in serine proteases: investigations of a G555E (GLY193 in chymotrypsin) mutant of blood coagulation factor XI. J Biol Chem 279: 29485–29492.

    Article  CAS  PubMed  Google Scholar 

  • Seeds NW, Basham ME, Ferguson JE. 2003. Absence of tissue plasminogen activator gene or activity impairs mouse cerebellar motor learning. J Neurosci 23: 7368–7375.

    CAS  PubMed  Google Scholar 

  • Selkoe DJ. 1991. Alzheimer's disease. In the beginning. Nature 354: 432–433.

    Article  CAS  PubMed  Google Scholar 

  • Semenza GL. 2001. HIF-1 and mechanisms of hypoxia sensing. Curr Opin Cell Biol 13: 167–171.

    Article  CAS  PubMed  Google Scholar 

  • Semenza GL, Agani F, Feldser D, Iyer N, Kotch L, et al. 2000. Hypoxia, HIF-1, and the pathophysiology of common human diseases. Adv Exp Med Biol 475: 123–130.

    Article  CAS  PubMed  Google Scholar 

  • Shan JD, Porvari K, Ruokonen M, Karhu A, Launonen V, et al. 1997. Steroid-involved transcriptional regulation of human genes encoding prostatic acid phosphatase, prostate-specific antigen, and prostate-specific glandular kallikrein. Endocrinology 138: 3764–3770.

    Article  CAS  PubMed  Google Scholar 

  • Sheehan JJ, Tsirka SE. 2005. Fibrin-modifying serine proteases thrombin, tPA, and plasmin in ischemic stroke: A review. Glia. 50: 340–350.

    Article  PubMed  Google Scholar 

  • Shimizu-Okabe C, Yousef GM, Diamandis EP, Yoshida S, Shiosaka S, et al. 2001. Expression of the kallikrein gene family in normal and Alzheimer's disease brain. Neuroreport 12: 2747–2751.

    Article  CAS  PubMed  Google Scholar 

  • Siess W, Lapetina EG. 1989. Prostacyclin inhibits platelet aggregation induced by phorbol ester or Ca2+ ionophore at steps distal to activation of protein kinase C and Ca2+-dependent protein kinases. Biochem 258: 57–65.

    CAS  Google Scholar 

  • Smith-Swintosky VL, Cheo-Isaacs CT, D'Andrea MR, Santulli RJ, Darrow AL, et al. 1997. Protease-activated receptor-2 (PAR-2) is present in the rat hippocampus and is associated with neurodegeneration. J Neurochem 69: 1890–1896.

    Article  CAS  PubMed  Google Scholar 

  • Sondell B, Dyberg P, Anneroth GK, Ostman PO, Egelrud T. 1996. Association between expression of stratum corneum chymotryptic enzyme and pathological keratinization in human oral mucosa. Acta Derm Venereol 76: 177–181.

    CAS  PubMed  Google Scholar 

  • Soreq H, Miskin R. 1981. Plasminogen activator in the rodent brain. Brain Res 216: 361–74.

    Article  CAS  PubMed  Google Scholar 

  • Soreq H, Miskin R. 1983. Plasminogen activator in the developing rat cerebellum: Biosynthesis and localization in granular neurons. Brain Res 313: 149–158.

    CAS  PubMed  Google Scholar 

  • Sumi Y, Dent MA, Owen DE, Seeley PJ, Morris RJ. 1992. The expression of tissue and urokinase-type plasminogen activators in neural development suggests different modes of proteolytic involvement in neuronal growth. Development 116: 625–637.

    CAS  PubMed  Google Scholar 

  • Suo Z, Citron BA, Festoff BW. 2004. Thrombin: A potential proinflammatory mediator in neurotrauma and neurodegenerative disorders. Curr Drug Targets Inflamm Allergy3: 105–114.

    Article  CAS  PubMed  Google Scholar 

  • Suzuki J, Yoshida S, Chen ZL, Momota Y, Kato K, et al. 1995. Ontogeny of neuropsin mRNA expression in the mouse brain. Neurosci Res 23: 345–351.

    Article  CAS  PubMed  Google Scholar 

  • Szilágyi L, Kénesi E, Katona G, Kaslik G, Juhász G, et al. 2001. Comparative in vitro studies on native and recombinant human cationic trypsins. Cathepsin B is a possible pathological activator of trypsinogen in pancreatitis. J Biol Chem 276: 24574–24580.

    Article  PubMed  Google Scholar 

  • Szmola R, Kukor Z, Sahin-Tóth M. 2003. Human mesotrypsin is a unique digestive protease specialized for the degradation of trypsin inhibitors. J Biol Chem 278: 48580–48589.

    Article  CAS  PubMed  Google Scholar 

  • Tang J, Yu CL, Williams SR, Springman E, Jeffery D, et al. 2005. Expression, crystallization, and three-dimensional structure of the catalytic domain of human plasma kallikrein. J Biol Chem 280: 41077–41089.

    Article  CAS  PubMed  Google Scholar 

  • Tanimoto H, Underwood LJ, Shigemasa K, Yan Yan MS, Clarke J, et al. 1999. The stratum corneum chymotryptic enzyme that mediates shedding and desquamation of skin cells is highly overexpressed in ovarian tumor cells. Cancer 86: 2074–2082.

    Article  CAS  PubMed  Google Scholar 

  • Tapparelli C, Metternich R, Ehrhardt C, Cook NS. 1993. Synthetic low-molecular weight thrombin inhibitors: Molecular design and pharmacological profile. Trends Pharmacol Sci 14: 366–376.

    Article  CAS  PubMed  Google Scholar 

  • Terayama R, Bando Y, Jiang YP, Mitrovic B, Yoshida S. 2005. Differential expression of protease M/neurosin in oligodendrocytes and their progenitors in an animal model of multiple sclerosis. Neurosci Lett 382: 82–87.

    Article  CAS  PubMed  Google Scholar 

  • Terayama R, Bando Y, Takahashi T, Yoshida S. 2004. Differential expression of neuropsin and protease M/neurosin in oligodendrocytes after injury to the spinal cord. Glia 48: 91–101.

    Article  PubMed  Google Scholar 

  • Timm DE. 1997. The crystal structure of the mouse glandular kallikrein-13 (prorenin converting enzyme). Protein Sci 6: 1418–1425.

    Article  CAS  PubMed  Google Scholar 

  • Tóth J, Gombos L, Simon Z, Medveczky P, Szilágyi L, et al. 2006. Thermodynamic analysis reveals structural rearrangement during the acylation step in human trypsin 4 on 4-methylumbelliferyl 4-guanidinobenzoate substrate analogue. J Biol Chem 281: 12596-12602.

    Google Scholar 

  • Tóth J, Simon Z, Medveczky P, Gombos L, Jelinek B, Szilágyi L, Gráf L, Málnási-Csizmadia A. 2006. Site directed mutagenesis at position 193 of human trypsin 4 alters the rate of conformational change during activation: role of local internal friction in protein dynamics. (under review in Proteins).

    Google Scholar 

  • Tsirka SE, Rogove AD, Bugge TH, Degen JL, Strickland S. 1997. An extracellular proteolytic cascade promotes neuronal degeneration in the mouse hippocampus. J Neurosci 17: 543–552.

    CAS  PubMed  Google Scholar 

  • Turgeon VL, Milligan CE, Houenou LJ. 1999. Activation of the protease-activated thrombin receptor (PAR)-1 induces motoneuron degeneration in the developing avian embryo. J Neuropathol Exp Neurol 58: 499–504.

    Article  CAS  PubMed  Google Scholar 

  • Turgeon VL, Houenou LJ. 1997. The role of thrombin-like serine proteases in the development, plasticity and pathology of the nervous system. Brain Res Rev 25: 85–95.

    Article  CAS  PubMed  Google Scholar 

  • Turgeon VL, Lloyd ED, Wang S, Festoff BW, Houenou LJ. 1998. Thrombin perturbs neurite outgrowth and induces apoptotic cell death in enriched chick spinal motoneuron cultures through caspase activation. J Neurosci 18: 6882–6891.

    CAS  PubMed  Google Scholar 

  • Vu TH, Hung DT, Wheaton VI, Coughlin SR. 1991. Molecular cloning of a functional thrombin receptor reveals a novel proteolytic mechanism of receptor activation. Cell 64: 1057–1068.

    Article  CAS  PubMed  Google Scholar 

  • Wang D, Bode W, Huber R. 1985. Bovine chymotrypsinogen A X-ray crystal structure analysis and refinement of a new crystal form at 1.8 A resolution. J Mol Biol 185: 595–624.

    Article  CAS  PubMed  Google Scholar 

  • Wang K, Gan L, Lee I, Hood L. 1995. Isolation and characterization of the chicken trypsinogen gene family 12. Biochem J 307: 471–479.

    CAS  PubMed  Google Scholar 

  • Wang X, Terzyan S, Tang J, Loy JA, Lin X, et al. 2000. Human plasminogen catalytic domain undergoes an unusual conformational change upon activation. J Mol Biol 295: 903–914.

    Article  CAS  PubMed  Google Scholar 

  • Ware JH, Dibenedetto AJ, Pittman RN. 1995. Localization of tissue plasminogen activator mRNA in adult rat brain. Brain Res Bull 37: 275–281.

    Article  CAS  PubMed  Google Scholar 

  • Weinstein JR, Gold SJ, Cunningham DD, Gall CM. 1995. Cellular localization of thrombin receptor mRNA in rat brain: Expression by mesencephalic dopaminergic neurons and codistribution with prothrombin mRNA. J Neurosci 15: 2906–2919.

    CAS  PubMed  Google Scholar 

  • Wiegand U, Corbach S, Minn A, Kang J, Müller-Hill B. 1993. Cloning of the cDNA encoding human brain trypsinogen and characterization of its product. Gene 136: 167–175.

    Article  CAS  PubMed  Google Scholar 

  • Wu YP, Siao CJ, Lu W, Sung TC, Frohman MA, et al. 2000. The tissue plasminogen activator (tPA)/plasmin extracellular proteolytic system regulates seizure-induced hippocampal mossy fiber outgrowth through a proteoglycan substrate. J Cell Biol 148: 1295–1304.

    Article  CAS  PubMed  Google Scholar 

  • Xi G, Wagner KR, Keep RF, Hua Y, de Courten-Myers GM, et al. 1998. Role of blood clot formation on early edema development after experimental intracerebral hemorrhage. Stroke 29: 2580–2585.

    CAS  PubMed  Google Scholar 

  • Xia CF, Yin H, Borlongan CV, Chao L, Chao J. 2004. Kallikrein gene transfer protects against ischemic stroke by promoting glial cell migration and inhibiting apoptosis. Hypertension 43: 452–459.

    Article  CAS  PubMed  Google Scholar 

  • Yamamoto M, Sawaya R, Mohanam S, Bindal AK, Bruner JM, et al. 1994a. Expression and localization of urokinase-type plasminogen activator in human astrocytomas in vivo. Cancer Res. 54: 3656–3661.

    CAS  Google Scholar 

  • Yamamoto M, Sawaya R, Mohanam S, Rao VH, Bruner JM, et al. 1994b. Activities, localizations, and roles of serine proteases and their inhibitors in human brain tumor progression. J Neurooncol. 22: 139–151.

    Article  CAS  Google Scholar 

  • Yamanaka H, He X, Matsumoto K, Shiosaka S, Yoshida S, 1999. Protease M/neurosin mRNA is expressed in mature oligodendrocytes. Brain Res. Mol. Brain Res. 71, 217–224.

    Article  CAS  PubMed  Google Scholar 

  • Yamashiro K, Tsuruoka N, Kodama S, Tsujimoto M, Yamamura Y, et al. 1997. Molecular cloning of a novel trypsin-like serine protease (neurosin) preferentially expressed in brain. Biochim. Biophys. Acta 1350, 11–14.

    CAS  PubMed  Google Scholar 

  • Yoshida S, Taniguchi M, Hirata A, Shiosaka S. 1998a. Sequence analysis and expression of human neuropsin cDNA and gene. Gene 213, 9–16.

    Article  CAS  Google Scholar 

  • Yoshida S, Taniguchi M, Suemoto T, Oka T, He X, et al. 1998b. cDNA cloning and expression of a novel serine protease, TLSP. Biochim. Biophys. Acta 1399, 225–228.

    CAS  Google Scholar 

  • Yousef GM, Diamandis EP. 1999. The new kallikrein-like gene, KLK-L2. Molecular characterization, mapping, tissue expression, and hormonal regulation. J. Biol. Chem. 274, 37511–37516.

    Article  CAS  PubMed  Google Scholar 

  • Yousef GM, Diamandis EP. 2000. The expanded human kallikrein gene family: locus characterization and molecular cloning of a new member, KLK-L3 (KLK9). Genomics 65, 184–194.

    Article  CAS  PubMed  Google Scholar 

  • Yousef GM, Diamandis EP. 2001. The new human tissue kallikrein gene family: Structure, function, and association to disease. Endocr Rev 22: 184–204.

    Article  CAS  PubMed  Google Scholar 

  • Yousef GM, Diamandis EP. 2002a. Expanded human tissue kallikrein family-a novel panel of cancer biomarkers. Tumour Biol 23: 185–192.

    Article  CAS  Google Scholar 

  • Yousef GM, Diamandis EP. 2002b. Human tissue kallikreins: A new enzymatic cascade pathway? Biol Chem 383: 1045–1057.

    Article  CAS  Google Scholar 

  • Yousef GM, Diamandis EP. 2002c. Kallikreins, steroid hormones and ovarian cancer: Is there a link? Minerva Endocrinol 27: 157–166.

    CAS  Google Scholar 

  • Yousef GM, Diamandis EP. 2003a. An overview of the kallikrein gene families in humans and other species: emerging candidate tumor markers. Clin Biochem 36: 443–452.

    Article  CAS  Google Scholar 

  • Yousef GM, Diamandis EP. 2003b. Tissue kallikreins: New players in normal and abnormal cell growth? Thromb Haemost 90: 7–16.

    CAS  Google Scholar 

  • Yousef GM, Kishi T, Diamandis EP. 2003. Role of kallikrein enzymes in the central nervous system. Clin Chim Acta 329: 1–8.

    Article  CAS  PubMed  Google Scholar 

  • Yousef GM, Kyriakopoulou LG, Scorilas A, Fracchioli S, Ghiringhello B, et al. 2001a. Quantitative expression of the human kallikrein gene 9 (KLK9) in ovarian cancer: A new independent and favorable prognostic marker. Cancer Res 61: 7811–7818.

    CAS  Google Scholar 

  • Yousef GM, Luo LY, Scherer SW, Sotiropoulou G, Diamandis EP. 1999. Molecular characterization of zyme/protease M/neurosin (PRSS9), a hormonally regulated kallikrein-like serine protease. Genomics 62: 251–259.

    Article  CAS  PubMed  Google Scholar 

  • Yousef GM, Magklara A, Chang A, Jung K, Katsaros D, et al. 2001b. Cloning of a new member of the human kallikrein gene family, KLK14, which is down-regulated in different malignancies. Cancer Res 61: 3425–3431.

    CAS  Google Scholar 

  • Yousef GM, Magklara A, Diamandis EP. 2000a. KLK12 is a novel serine protease and a new member of the human kallikrein gene family-differential expression in breast cancer. Genomics 69: 331–341.

    Article  CAS  Google Scholar 

  • Yousef GM, Obiezu CV, Luo LY, Magklara A, Borgono CA, et al. 2005. Human tissue kallikreins: From gene structure to function and clinical applications. Adv Clin Chem 39: 11–79.

    Article  PubMed  Google Scholar 

  • Yousef GM, Scorilas A, Diamandis EP. 2000b. Genomic organization, mapping, tissue expression, and hormonal regulation of trypsin-like serine protease (TLSP PRSS20), a new member of the human kallikrein gene family. Genomics 63: 88–96.

    Article  CAS  Google Scholar 

  • Yousef GM, Scorilas A, Kyriakopoulou LG, Rendl L, Diamandis M, et al. 2002. Human kallikrein gene 5 (KLK5) expression by quantitative PCR: an independent indicator of poor prognosis in breast cancer. Clin Chem 48: 1241–1250.

    CAS  PubMed  Google Scholar 

  • Yousef GM, Scorilas A, Magklara A, Soosaipillai A, Diamandis EP, 2000c. The KLK7 (PRSS6) gene, encoding for the stratum corneum chymotryptic enzyme is a new member of the human kallikrein gene family - genomic characterization, mapping, tissue expression and hormonal regulation. Gene 254: 119–128.

    Article  CAS  Google Scholar 

  • Zarghooni M, Soosaipillai A, Grass L, Scorilas A, Mirazimi N, et al. 2002. Decreased concentration of human kallikrein 6 in brain extracts of Alzheimer's disease patients. Clin Biochem 35: 225–231.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by a Hungarian Scientific Research Fund grant OTKA to L. Gráf (T047154, TS 049812), L. Szilágyi (T037568), and to J. Gergely (TS 0044711). The huge volume of literature in the field of serine proteases made it impossible to cite every study in this review. As such, the authors would like to apologize to their colleagues for any unintentional oversight or omission of their studies.

Authors
  1. J. Tóth
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. P. Medveczky
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. L. Szilágyi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. L. Gráf
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Center for Neurochemistry, Nathan S. Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, Orangeburg, Newyork, 10962, USA

    Abel Lajtha (Director) (Director)

  2. Department of Neurosciences Division of Neurology, Medical University of South Carolina, 96 Jonathan Lucas Street Suite 309, Charleston, SC 29425, USA

    Naren Banik (Professor) (Professor)

Rights and permissions

Reprints and permissions

Copyright information

© 2007 Springer Science+Business Media, LLC

About this entry

Cite this entry

Tóth, J., Medveczky, P., Szilágyi, L., Gráf, L. (2007). Serine Proteases. In: Lajtha, A., Banik, N. (eds) Handbook of Neurochemistry and Molecular Neurobiology. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-30379-6_14

Download citation

Publish with us

Policies and ethics

Search

Navigation