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Transglutaminases and receptor tyrosine kinases

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Abstract

Transglutaminases are confounding enzymes which are known to play key roles in various cellular processes. In this paper, we aim to bring together several pieces of evidence from published research and literature that suggest a potentially vital role for transglutaminases in receptor tyrosine kinases (RTK) signalling. We cite literature that confirms and suggests the formation of integrin:RTK:transglutaminase complexes and explores the occurrence and functionality of these complexes in a large fraction of the RTK family.

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References

  • Aeschlimann D, Paulsson M (1991) Cross-linking of laminin-nidogen complexes by tissue transglutaminase: a novel mechanism for basement membrane stabilization. J Biol Chem 266:15308–15317

    PubMed  CAS  Google Scholar 

  • Akimov SS, Belkin AM (2001) Cell-surface transglutaminase promotes fibronectin assembly via interaction with the gelatin-binding domain of fibronectin: a role in TGF{beta}-dependent matrix deposition. J Cell Sci 114:2989–3000

    PubMed  CAS  Google Scholar 

  • Akimov SS, Krylov D, Fleischman LF, Belkin AM (2000) Tissue transglutaminase is an integrin-binding adhesion coreceptor for fibronectin. J Cell Biol 148:825–838

    Article  PubMed  CAS  Google Scholar 

  • Alford SC, Bazowski J, Lorimer H, Elowe S, Howard PL (2007) Tissue transglutaminase clusters soluble A-type ephrins into functionally active high molecular weight oligomers. Exp Cell Res 313:4170–4179

    Article  PubMed  CAS  Google Scholar 

  • Antonyak MA, McNeill CJ, Wakshlag JJ, Boehm JE, Cerione RA (2003) Activation of the Ras-ERK pathway inhibits retinoic acid-induced stimulation of tissue transglutaminase expression in NIH3T3 cells. J Biol Chem 278:15859–15866

    Article  PubMed  CAS  Google Scholar 

  • Antonyak MA, Miller AM, Jansen JM, Boehm JE, Balkman CE, Wakshlag JJ, Page RL, Cerione RA (2004) Augmentation of tissue transglutaminase expression and activation by epidermal growth factor inhibit doxorubicin-induced apoptosis in human breast cancer cells. J Biol Chem 279:41461–41467

    Article  PubMed  CAS  Google Scholar 

  • Arai F, Hirao A, Ohmura M, Sato H, Matsuoka S, Takubo K, Ito K, Koh GY, Suda T (2004) Tie2/Angiopoietin-1 signaling regulates hematopoietic stem cell quiescence in the bone marrow niche. Cell 118:149–161

    Article  PubMed  CAS  Google Scholar 

  • Bokel C, Brown NH (2002) Integrins in development: moving on, responding to, and sticking to the extracellular matrix. Dev Cell 3:311–321

    Article  PubMed  CAS  Google Scholar 

  • Bowness JM, Folk JE, Timpl R (1987) Identification of a substrate site for liver transglutaminase on the aminopropeptide of type III collagen. J Biol Chem 262:1022–1024

    PubMed  CAS  Google Scholar 

  • Clemmons DR, Maile LA (2005) Interaction between insulin-like growth factor-I receptor and alphavbeta3 integrin linked signaling pathways: cellular responses to changes in multiple signaling inputs. Mol Endocrinol 19:1–11

    Article  PubMed  CAS  Google Scholar 

  • Dardik R, Inbal A (2006) Complex formation between tissue transglutaminase II (tTG) and vascular endothelial growth factor receptor 2 (VEGFR-2): proposed mechanism for modulation of endothelial cell response to VEGF. Exp Cell Res 312:2973–2982

    Article  PubMed  CAS  Google Scholar 

  • Dardik R, Loscalzo J, Eskaraev R, Inbal A (2005) Molecular mechanisms underlying the proangiogenic effect of factor XIII. Arterioscler Thromb Vasc Biol 25:526–532

    Article  PubMed  CAS  Google Scholar 

  • Dieterich W, Esslinger B, Trapp D, Hahn E, Huff T, Seilmeier W, Wieser H, Schuppan D (2006) Cross linking to tissue transglutaminase and collagen favours gliadin toxicity in coeliac disease. Gut 55:478–484

    Article  PubMed  CAS  Google Scholar 

  • Doerr ME, Jones JI (1996) The roles of integrins and extracellular matrix proteins in the insulin-like growth factor I-stimulated chemotaxis of human breast cancer cells. J Biol Chem 271:2443–2447

    Article  PubMed  CAS  Google Scholar 

  • Falcioni R, Antonini A, Nistico P, Di Stefano S, Crescenzi M, Natali PG, Sacchi A (1997) Alpha 6 beta 4 and alpha 6 beta 1 integrins associate with ErbB-2 in human carcinoma cell lines. Exp Cell Res 236:76–85

    Article  PubMed  CAS  Google Scholar 

  • Fesus L, Piacentini M (2002) Transglutaminase 2: an enigmatic enzyme with diverse functions. Trends Biochem Sci 27:534–539

    Article  PubMed  CAS  Google Scholar 

  • Goel HL, Breen M, Zhang J, Das I, Aznavoorian-Cheshire S, Greenberg NM, Elgavish A, Languino LR (2005) {beta}1A integrin expression is required for type 1 insulin-like growth factor receptor mitogenic and transforming activities and localization to focal contacts. Cancer Res 65:6692–6700

    Article  PubMed  CAS  Google Scholar 

  • Holder N, Klein R (1999) Eph receptors and ephrins: effectors of morphogenesis. Development 126:2033–2044

    PubMed  CAS  Google Scholar 

  • Hollier BG, Kricker JA, Van Lonkhuyzen DR, Leavesley DI, Upton Z (2008) Substrate-bound insulin-like growth factor (IGF)-I-IGF binding protein-vitronectin-stimulated breast cell migration is enhanced by coactivation of the phosphatidylinositide 3-kinase/AKT pathway by {alpha}v-integrins and the IGF-I receptor. Endocrinology 149:1075–1090

    Article  PubMed  CAS  Google Scholar 

  • Jeitner TM, Pinto JT, Krasnikov BF, Horswill M, Cooper AJL (2009) Transglutaminases and neurodegeneration. J Neurochem 109:160–166

    Article  PubMed  CAS  Google Scholar 

  • Kaartinen MT, Pirhonen A, Linnala-Kankkunen A, Maenpaa PH (1997) Transglutaminase-catalyzed cross-linking of osteopontin is inhibited by osteocalcin. J Biol Chem 272:22736–22741

    Article  PubMed  CAS  Google Scholar 

  • Kang SK, Yi KS, Kwon NS, Park KH, Kim UH, Baek KJ, Im MJ (2004) Alpha1B-adrenoceptor signaling and cell motility: GTPase function of Gh/transglutaminase 2 inhibits cell migration through interaction with cytoplasmic tail of integrin alpha subunits. J Biol Chem 279:36593–36600

    Article  PubMed  CAS  Google Scholar 

  • Kashyap AS, Hollier BG, Manton KJ, Satyamoorthy K, Leavesley DI, Upton Z (2011) Insulin-like growth factor-I:vitronectin complex-induced changes in gene expression effect breast cell survival and migration. Endocrinology 152:1388–1401

    Article  PubMed  CAS  Google Scholar 

  • Kiely PA, O’Gorman D, Luong K, Ron D, O’Connor R (2006) Insulin-like growth factor I controls a mutually exclusive association of RACK1 with protein phosphatase 2A and {beta}1 integrin to promote cell migration. Mol Cell Biol 26:4041–4051

    Article  PubMed  CAS  Google Scholar 

  • Kleman JP, Aeschlimann D, Paulsson M, van der Rest M (1995) Transglutaminase-catalyzed cross-linking of fibrils of collagen V/XI in A204 rhabdomyosarcoma cells. Biochemistry 34:13768–13775

    Article  PubMed  CAS  Google Scholar 

  • Kotani N, Gu J, Isaji T, Udaka K, Taniguchi N, Honke K (2008) Biochemical visualization of cell surface molecular clustering in living cells. Proc Natl Acad Sci 105:7405–7409

    Article  PubMed  CAS  Google Scholar 

  • Kricker JA, Towne CL, Firth SM, Herington AC, Upton Z (2003) Structural and functional evidence for the interaction of insulin-like growth factors (IGFs) and IGF binding proteins with vitronectin. Endocrinology 144:2807–2815

    Article  PubMed  CAS  Google Scholar 

  • Legate KR, Wickstrom SA, Fassler R (2009) Genetic and cell biological analysis of integrin outside-in signaling. Genes Dev 23:397–418

    Article  PubMed  CAS  Google Scholar 

  • LeMosy EK, Erickson HP, Beyer WF Jr, Radek JT, Jeong JM, Murthy SN, Lorand L (1992) Visualization of purified fibronectin-transglutaminase complexes. J Biol Chem 267:7880–7885

    PubMed  CAS  Google Scholar 

  • Lorand L, Graham RM (2003) Transglutaminases: crosslinking enzymes with pleiotropic functions. Nat Rev Mol Cell Biol 4:140–156

    Article  PubMed  CAS  Google Scholar 

  • Maile LA, Busby WH, Sitko K, Capps BE, Sergent T, Badley-Clarke J, Ling Y, Clemmons DR (2006) The heparin binding domain of vitronectin is the region that is required to enhance insulin-like growth factor-I signaling. Mol Endocrinol 20:881–892

    Article  PubMed  CAS  Google Scholar 

  • Martino MM, Hubbell JA (2010) The 12th–14th type III repeats of fibronectin function as a highly promiscuous growth factor-binding domain. FASEB J 24:4711–4721

    Article  PubMed  CAS  Google Scholar 

  • Maruko A, Ohtake Y, Katoh S, Ohkubo Y (2009) Transglutaminase down-regulates the dimerization of epidermal growth factor receptor in rat perivenous and periportal hepatocytes. Cell Prolif 42:647–656

    Article  PubMed  CAS  Google Scholar 

  • Mehta K, Kumar A, Kim HI (2010) Transglutaminase 2: a multi-tasking protein in the complex circuitry of inflammation and cancer. Biochem Pharmacol 80:1921–1929

    Article  PubMed  CAS  Google Scholar 

  • Moro L, Venturino M, Bozzo C, Silengo L, Altruda F, Beguinot L, Tarone G, Defilippi P (1998) Integrins induce activation of EGF receptor: role in MAP kinase induction and adhesion-dependent cell survival. EMBO J 17:6622–6632

    Article  PubMed  CAS  Google Scholar 

  • Ricono JM, Huang M, Barnes LA, Lau SK, Weis SM, Schlaepfer DD, Hanks SK, Cheresh DA (2009) Specific cross-talk between epidermal growth factor receptor and integrin {alpha}v{beta}5 promotes carcinoma cell invasion and metastasis. Cancer Res 69:1383–1391

    Article  PubMed  CAS  Google Scholar 

  • Robinson DR, Wu YM, Lin SF (2000) The protein tyrosine kinase family of the human genome. Oncogene 19:5548–5557

    Article  PubMed  CAS  Google Scholar 

  • Samani AA, Yakar S, LeRoith D, Brodt P (2007) The role of the IGF system in cancer growth and metastasis: overview and recent insights. Endocr Rev 28:20–47

    Article  PubMed  CAS  Google Scholar 

  • Sane DC, Moser TL, Pippen AM, Parker CJ, Achyuthan KE, Greenberg CS (1988) Vitronectin is a substrate for transglutaminases. Biochem Biophys Res Commun 157:115–120

    Article  PubMed  CAS  Google Scholar 

  • Schneller M, Vuori K, Ruoslahti E (1997) [alpha]v[beta]3 integrin associates with activated insulin and PDGF[beta] receptors and potentiates the biological activity of PDGF. EMBO J 16:5600–5607

    Article  PubMed  CAS  Google Scholar 

  • Somanath P, Ciocea A, Byzova T (2009) Integrin and growth factor receptor alliance in angiogenesis. Cell Biochem Biophys 53:53–64

    Article  PubMed  CAS  Google Scholar 

  • Toth B, Garabuczi E, Sarang Z, Vereb G, Vamosi G, Aeschlimann D, Blasko B, Becsi B, Erdodi F, Lacy-Hulbert A, Zhang A, Falasca L, Birge RB, Balajthy Z, Melino G, Fesus L, Szondy Z (2009) Transglutaminase 2 is needed for the formation of an efficient phagocyte portal in macrophages engulfing apoptotic cells. J Immunol 182:2084–2092

    Article  PubMed  CAS  Google Scholar 

  • Upton Z, Cuttle L, Noble A, Kempf M, Topping G, Malda J, Xie Y, Mill J, Harkin DG, Kravchuk O, Leavesley DI, Kimble RM (2008) Vitronectin: growth factor complexes hold potential as a wound therapy approach. J Invest Dermatol 128:1535–1544

    Article  PubMed  CAS  Google Scholar 

  • Van Lonkhuyzen DR, Hollier BG, Shooter GK, Leavesley DI, Upton Z (2007) Chimeric vitronectin:insulin-like growth factor proteins enhance cell growth and migration through co-activation of receptors. Growth Factors 25:295–308

    Article  PubMed  Google Scholar 

  • Vuori K, Ruoslahti E (1994) Association of insulin receptor substrate-1 with integrins. Science 266:1576–1578

    Article  PubMed  CAS  Google Scholar 

  • Zemskov EA, Janiak A, Hang J, Waghray A, Belkin AM (2006) The role of tissue transglutaminase in cell–matrix interactions. Frontiers Biosci 11:1057–1076

    Article  CAS  Google Scholar 

  • Zemskov EA, Loukinova E, Mikhailenko I, Coleman RA, Strickland DK, Belkin AM (2009) Regulation of platelet-derived growth factor receptor function by integrin-associated cell surface transglutaminase. J Biol Chem 284:16693–16703

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

Queensland University of Technology has filed a patent related to Transglutaminases and insulin-like growth factors. An inventorship audit is underway and all the authors of this paper may be deemed inventors. Tissue Therapies Ltd, a company spun out of Queensland University of Technology, has a license to commercialize this intellectual property. Z.U holds shares in and is a consultant for Tissue Therapies Ltd.

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Authors and Affiliations

  1. Tissue Repair and Regeneration Program, Institute of Health and Biomedical Innovation, Queensland University of Technology, 60 Musk Ave, Kelvin Grove Qld, 4059, Australia

    Manaswini Sivaramakrishnan, Gary K. Shooter, Zee Upton & Tristan I. Croll

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  1. Manaswini Sivaramakrishnan
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  2. Gary K. Shooter
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  3. Zee Upton
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  4. Tristan I. Croll
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Correspondence to Manaswini Sivaramakrishnan.

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Sivaramakrishnan, M., Shooter, G.K., Upton, Z. et al. Transglutaminases and receptor tyrosine kinases. Amino Acids 44, 19–24 (2013). https://doi.org/10.1007/s00726-011-1113-x

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  • DOI: https://doi.org/10.1007/s00726-011-1113-x

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