Journal of Cell Communication and Signaling

, Volume 7, Issue 4, pp 301–307 | Cite as

A network map of BDNF/TRKB and BDNF/p75NTR signaling system

  • Varot K. Sandhya
  • Rajesh Raju
  • Renu Verma
  • Jayshree Advani
  • Rakesh Sharma
  • Aneesha Radhakrishnan
  • Vishalakshi Nanjappa
  • Jayasuryan Narayana
  • B. L. Somani
  • Kanchan K. Mukherjee
  • Akhilesh Pandey
  • Rita Christopher
  • T. S. Keshava Prasad
Nuts and Bolts

Abbreviations

BDNF

Brain-derived neurotrophic factor

TRK

Tropomyosin-related kinase

NGF

Nerve growth factor

NT

Neurotrophin

p75NTR

p75 neurotrophin receptor

PPIs

Protein–protein interactions

PTMs

Post-translational modifications

BioPAX

Biological PAthway eXchange

SBML

Systems Biology Markup Language

PSI-MI

Proteomics Standards Initiative for Molecular Interaction

References

  1. Allen SJ, Dawbarn D, Eckford SD, Wilcock GK, Ashcroft M, Colebrook SM, Feeney R, MacGowan SH (1994) Cloning of a non-catalytic form of human trkB and distribution of messenger RNA for trkB in human brain. Neuroscience 60:825–834PubMedCrossRefGoogle Scholar
  2. Araki T, Yamada M, Ohnishi H, Sano SI, Hatanaka H (2000) BIT/SHPS-1 enhances brain-derived neurotrophic factor-promoted neuronal survival in cultured cerebral cortical neurons. J Neurochem 75:1502–1510PubMedCrossRefGoogle Scholar
  3. Barbacid M (1995) Neurotrophic factors and their receptors. Curr Opin Cell Biol 7:148–155PubMedCrossRefGoogle Scholar
  4. Barde YA, Edgar D, Thoenen H (1982) Purification of a new neurotrophic factor from mammalian brain. EMBO J 1:549–553PubMedCentralPubMedGoogle Scholar
  5. Binder DK, Scharfman HE (2004) Brain-derived neurotrophic factor. Growth Factors 22:123–131PubMedCentralPubMedCrossRefGoogle Scholar
  6. Burke MA, Bothwell M (2003) p75 neurotrophin receptor mediates neurotrophin activation of NF-kappa B and induction of iNOS expression in P19 neurons. J Neurobiol 55:191–203PubMedCrossRefGoogle Scholar
  7. Chao MV, Bothwell MA, Ross AH, Koprowski H, Lanahan AA, Buck CR, Sehgal A (1986) Gene transfer and molecular cloning of the human NGF receptor. Science 232:518–521PubMedCrossRefGoogle Scholar
  8. Cheng PL, Song AH, Wong YH, Wang S, Zhang X, Poo MM (2011) Self-amplifying autocrine actions of BDNF in axon development. Proc Natl Acad Sci U S A 108:18430–18435PubMedCentralPubMedCrossRefGoogle Scholar
  9. David MD, Yeramian A, Dunach M, Llovera M, Canti C, de Herreros AG, Comella JX, Herreros J (2008) Signalling by neurotrophins and hepatocyte growth factor regulates axon morphogenesis by differential beta-catenin phosphorylation. J Cell Sci 121:2718–2730PubMedCrossRefGoogle Scholar
  10. Demir E, Cary MP, Paley S, Fukuda K, Lemer C, Vastrik I, Wu G, D’Eustachio P, Schaefer C et al (2010) The BioPAX community standard for pathway data sharing. Nat Biotechnol 28:935–942PubMedCentralPubMedCrossRefGoogle Scholar
  11. Dey G, Radhakrishnan A, Syed N, Thomas JK, Nadig A, Srikumar K, Mathur PP, Pandey A, Lin SK et al (2012) Signaling network of Oncostatin M pathway. J Cell Commun Signal. doi:10.1007/s12079-012-0186-y
  12. Ferrer I, Marin C, Rey MJ, Ribalta T, Goutan E, Blanco R, Tolosa E, Marti E (1999) BDNF and full-length and truncated TrkB expression in Alzheimer disease. Implications in therapeutic strategies. J Neuropathol Exp Neurol 58:729–739PubMedCrossRefGoogle Scholar
  13. Finkbeiner S, Tavazoie SF, Maloratsky A, Jacobs KM, Harris KM, Greenberg ME (1997) CREB: a major mediator of neuronal neurotrophin responses. Neuron 19:1031–1047PubMedCrossRefGoogle Scholar
  14. Goel R, Harsha HC, Pandey A, Prasad TSK (2012a) Human Protein Reference Database and Human Proteinpedia as resources for phosphoproteome analysis. Mol Biosyst 8:453–463PubMedCentralPubMedCrossRefGoogle Scholar
  15. Goel R, Raju R, Maharudraiah J, Kumar GSS, Ghosh K, Kumar A, Lashmi PT, Sharma J, Sharma R et al (2012b) A signaling network of thyroid-stimulating hormone. J Proteomics Bioinforma 4:238–241Google Scholar
  16. Groth RD, Mermelstein PG (2003) Brain-derived neurotrophic factor activation of NFAT (nuclear factor of activated T-cells)-dependent transcription: a role for the transcription factor NFATc4 in neurotrophin-mediated gene expression. J Neurosci 23:8125–8134PubMedGoogle Scholar
  17. Hall J, Thomas KL, Everitt BJ (2000) Rapid and selective induction of BDNF expression in the hippocampus during contextual learning. Nat Neurosci 3:533–535PubMedCrossRefGoogle Scholar
  18. Hermjakob H, Montecchi-Palazzi L, Bader G, Wojcik J, Salwinski L, Ceol A, Moore S, Orchard S, Sarkans U et al (2004) The HUPO PSI’s molecular interaction format—a community standard for the representation of protein interaction data. Nat Biotechnol 22:177–183PubMedCrossRefGoogle Scholar
  19. Hucka M, Finney A, Sauro HM, Bolouri H, Doyle JC, Kitano H, Arkin AP, Bornstein BJ, Bray D et al (2003) The systems biology markup language (SBML): a medium for representation and exchange of biochemical network models. Bioinformatics 19:524–531PubMedCrossRefGoogle Scholar
  20. Jadhav T, Geetha T, Jiang J, Wooten MW (2008) Identification of a consensus site for TRAF6/p62 polyubiquitination. Biochem Biophys Res Commun 371:521–524Google Scholar
  21. Jovanovic JN, Czernik AJ, Fienberg AA, Greengard P, Sihra TS (2000) Synapsins as mediators of BDNF-enhanced neurotransmitter release. Nat Neurosci 3:323–329PubMedCrossRefGoogle Scholar
  22. Kajiya M, Shiba H, Fujita T, Ouhara K, Takeda K, Mizuno N, Kawaguchi H, Kitagawa M, Takata T et al (2008) Brain-derived neurotrophic factor stimulates bone/cementum-related protein gene expression in cementoblasts. J Biol Chem 283:16259–16267PubMedCentralPubMedCrossRefGoogle Scholar
  23. Kandasamy K, Keerthikumar S, Raju R, Prasad TSK, Ramachandra YL, Mohan S, Pandey A (2009) PathBuilder—open source software for annotating and developing pathway resources. Bioinformatics 25:2860–2862PubMedCentralPubMedCrossRefGoogle Scholar
  24. Kandasamy K, Mohan SS, Raju R, Keerthikumar S, Kumar GS, Venugopal AK, Telikicherla D, Navarro JD, Mathivanan S et al (2010) NetPath: a public resource of curated signal transduction pathways. Genome Biol 11:R3PubMedCentralPubMedCrossRefGoogle Scholar
  25. Kaplan DR, Martin-Zanca D, Parada LF (1991) Tyrosine phosphorylation and tyrosine kinase activity of the trk proto-oncogene product induced by NGF. Nature 350:158–160PubMedCrossRefGoogle Scholar
  26. Kenchappa RS, Tep C, Korade Z, Urra S, Bronfman FC, Yoon SO, Carter BD (2010) p75 neurotrophin receptor-mediated apoptosis in sympathetic neurons involves a biphasic activation of JNK and up-regulation of tumor necrosis factor-alpha-converting enzyme/ADAM17. J Biol Chem 285:20358–20368PubMedCentralPubMedCrossRefGoogle Scholar
  27. Kim SH, Won SJ, Sohn S, Kwon HJ, Lee JY, Park JH, Gwag BJ (2002) Brain-derived neurotrophic factor can act as a pronecrotic factor through transcriptional and translational activation of NADPH oxidase. J Cell Biol 159:821–831PubMedCentralPubMedCrossRefGoogle Scholar
  28. Klein R, Parada LF, Coulier F, Barbacid M (1989) trkB, a novel tyrosine protein kinase receptor expressed during mouse neural development. EMBO J 8:3701–3709PubMedCentralPubMedGoogle Scholar
  29. Klein R, Nanduri V, Jing SA, Lamballe F, Tapley P, Bryant S, Cordon-Cardo C, Jones KR, Reichardt LF et al (1991) The trkB tyrosine protein kinase is a receptor for brain-derived neurotrophic factor and neurotrophin-3. Cell 66:395–403PubMedCentralPubMedCrossRefGoogle Scholar
  30. Lamballe F, Klein R, Barbacid M (1991) trkC, a new member of the trk family of tyrosine protein kinases, is a receptor for neurotrophin-3. Cell 66:967–979PubMedCrossRefGoogle Scholar
  31. Leibrock J, Lottspeich F, Hohn A, Hofer M, Hengerer B, Masiakowski P, Thoenen H, Barde YA (1989) Molecular cloning and expression of brain-derived neurotrophic factor. Nature 341:149–152PubMedCrossRefGoogle Scholar
  32. Lin G, Bella AJ, Lue TF, Lin CS (2006) Brain-derived neurotrophic factor (BDNF) acts primarily via the JAK/STAT pathway to promote neurite growth in the major pelvic ganglion of the rat: part 2. J Sex Med 3:821–827, discussion 828–829PubMedCrossRefGoogle Scholar
  33. Lindsay RM (1996) Role of neurotrophins and trk receptors in the development and maintenance of sensory neurons: an overview. Philos Trans R Soc Lond B Biol Sci 351:365–373PubMedCrossRefGoogle Scholar
  34. Lommatzsch M, Braun A, Mannsfeldt A, Botchkarev VA, Botchkareva NV, Paus R, Fischer A, Lewin GR, Renz H (1999) Abundant production of brain-derived neurotrophic factor by adult visceral epithelia. Implications for paracrine and target-derived Neurotrophic functions. Am J Pathol 155:1183–1193PubMedCentralPubMedCrossRefGoogle Scholar
  35. Martin-Zanca D, Hughes SH, Barbacid M (1986) A human oncogene formed by the fusion of truncated tropomyosin and protein tyrosine kinase sequences. Nature 319:743–748PubMedCrossRefGoogle Scholar
  36. Matthews VB, Astrom MB, Chan MH, Bruce CR, Krabbe KS, Prelovsek O, Akerstrom T, Yfanti C, Broholm C et al (2009) Brain-derived neurotrophic factor is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via activation of AMP-activated protein kinase. Diabetologia 52:1409–1418PubMedCrossRefGoogle Scholar
  37. Miyamoto Y, Yamauchi J, Tanoue A, Wu C, Mobley WC (2006) TrkB binds and tyrosine-phosphorylates Tiam1, leading to activation of Rac1 and induction of changes in cellular morphology. Proc Natl Acad Sci U S A 103:10444–10449PubMedCentralPubMedCrossRefGoogle Scholar
  38. Nakagawara A, Liu XG, Ikegaki N, White PS, Yamashiro DJ, Nycum LM, Biegel JA, Brodeur GM (1995) Cloning and chromosomal localization of the human TRK-B tyrosine kinase receptor gene (NTRK2). Genomics 25:538–546PubMedCrossRefGoogle Scholar
  39. Namekata K, Harada C, Guo X, Kimura A, Kittaka D, Watanabe H, Harada T (2012) Dock3 stimulates axonal outgrowth via GSK-3beta-mediated microtubule assembly. J Neurosci 32:264–274PubMedCrossRefGoogle Scholar
  40. Nanjappa V, Raju R, Muthusamy B, Sharma J, Thomas JK, Nidhina PAH, Harsha HC, Pandey A, Anilkumar G et al (2011) A comprehensive curated reaction map of leptin signaling pathway. J Proteomics Bioinforma 4:184–189Google Scholar
  41. Negro A, Tavella A, Grandi C, Skaper SD (1994) Production and characterization of recombinant rat brain-derived neurotrophic factor and neurotrophin-3 from insect cells. J Neurochem 62:471–478PubMedCrossRefGoogle Scholar
  42. Neves-Pereira M, Mundo E, Muglia P, King N, Macciardi F, Kennedy JL (2002) The brain-derived neurotrophic factor gene confers susceptibility to bipolar disorder: evidence from a family-based association study. Am J Hum Genet 71:651–655PubMedCentralPubMedCrossRefGoogle Scholar
  43. Ohira K, Shimizu K, Hayashi M (2001) TrkB dimerization during development of the prefrontal cortex of the macaque. J Neurosci Res 65:463–469PubMedCrossRefGoogle Scholar
  44. Ou LC, Gean PW (2006) Regulation of amygdala-dependent learning by brain-derived neurotrophic factor is mediated by extracellular signal-regulated kinase and phosphatidylinositol-3-kinase. Neuropsychopharmacology 31:287–296PubMedCrossRefGoogle Scholar
  45. Pezet S, Malcangio M, Lever IJ, Perkinton MS, Thompson SW, Williams RJ, McMahon SB (2002) Noxious stimulation induces Trk receptor and downstream ERK phosphorylation in spinal dorsal horn. Mol Cell Neurosci 21:684–695PubMedCrossRefGoogle Scholar
  46. Radhakrishnan A, Raju R, Tuladhar N, Subbannayya T, Thomas JK, Goel R, Telikicherla D, Palapetta SM, Rahiman BA et al (2012) A pathway map of prolactin signaling. J Cell Commun Signal 6:169–173PubMedCentralPubMedCrossRefGoogle Scholar
  47. Raju R, Balakrishnan L, Nanjappa V, Bhattacharjee M, Getnet D, Muthusamy B, Kurian Thomas J, Sharma J, Rahiman BA et al (2011a) A comprehensive manually curated reaction map of RANKL/RANK-signaling pathway. Database (Oxford) 2011:bar021Google Scholar
  48. Raju R, Nanjappa V, Balakrishnan L, Radhakrishnan A, Thomas JK, Sharma J, Tian M, Palapetta SM, Subbannayya T et al (2011b) NetSlim: high-confidence curated signaling maps. Database (Oxford) 2011:bar032Google Scholar
  49. Shalizi A, Lehtinen M, Gaudilliere B, Donovan N, Han J, Konishi Y, Bonni A (2003) Characterization of a neurotrophin signaling mechanism that mediates neuron survival in a temporally specific pattern. J Neurosci 23:7326–7336PubMedGoogle Scholar
  50. Soman S, Raju R, Sandhya VK, Advani J, Khan AA, Harsha HC, Prasad TSK, Sudhakaran PR, Pandey A et al (2013) A multicellular signal transduction network of AGE/RAGE signaling. J Cell Commun Signal 7:19–23PubMedCentralPubMedCrossRefGoogle Scholar
  51. Subbannayya T, Balakrishnan L, Sudarshan G, Advani J, Kumar S, Mahmood R, Nair B, Sirdeshmukh R, Mukherjee KK et al (2013) An integrated map of corticotropin-releasing hormone signaling pathway. J Cell Commun Signal. doi:10.1007/s12079-013-0197-3
  52. Sugimoto T, Kuroda H, Horii Y, Moritake H, Tanaka T, Hattori S (2001) Signal transduction pathways through TRK-A and TRK-B receptors in human neuroblastoma cells. Jpn J Cancer Res 92:152–160PubMedCrossRefGoogle Scholar
  53. Szatmari E, Kalita KB, Kharebava G, Hetman M (2007) Role of kinase suppressor of Ras-1 in neuronal survival signaling by extracellular signal-regulated kinase 1/2. J Neurosci 27:11389–11400PubMedCrossRefGoogle Scholar
  54. Takahashi M, Hayashi S, Kakita A, Wakabayashi K, Fukuda M, Kameyama S, Tanaka R, Takahashi H, Nawa H (1999) Patients with temporal lobe epilepsy show an increase in brain-derived neurotrophic factor protein and its correlation with neuropeptide Y. Brain Res 818:579–582PubMedCrossRefGoogle Scholar
  55. Takei N, Inamura N, Kawamura M, Namba H, Hara K, Yonezawa K, Nawa H (2004) Brain-derived neurotrophic factor induces mammalian target of rapamycin-dependent local activation of translation machinery and protein synthesis in neuronal dendrites. J Neurosci 24:9760–9769PubMedCrossRefGoogle Scholar
  56. Telikicherla D, Ambekar A, Palapetta SM, Dwivedi SB, Raju R, Sharma J, Prasad TSK, Ramachandra Y, Mohan SS et al (2011) A comprehensive curated resource for follicle stimulating hormone signaling. BMC Res Notes 4:408PubMedCentralPubMedCrossRefGoogle Scholar
  57. Thakker-Varia S, Alder J, Crozier RA, Plummer MR, Black IB (2001) Rab3A is required for brain-derived neurotrophic factor-induced synaptic plasticity: transcriptional analysis at the population and single-cell levels. J Neurosci 21:6782–6790PubMedGoogle Scholar
  58. Timmusk T, Palm K, Metsis M, Reintam T, Paalme V, Saarma M, Persson H (1993) Multiple promoters direct tissue-specific expression of the rat BDNF gene. Neuron 10:475–489PubMedCrossRefGoogle Scholar
  59. van Iersel MP, Kelder T, Pico AR, Hanspers K, Coort S, Conklin BR, Evelo C (2008) Presenting and exploring biological pathways with PathVisio. BMC Bioinforma 9:399CrossRefGoogle Scholar
  60. Wu K, Xu JL, Suen PC, Levine E, Huang YY, Mount HT, Lin SY, Black IB (1996) Functional trkB neurotrophin receptors are intrinsic components of the adult brain postsynaptic density. Brain Res Mol Brain Res 43:286–290PubMedCrossRefGoogle Scholar
  61. Wu K, Len GW, McAuliffe G, Ma C, Tai JP, Xu F, Black IB (2004) Brain-derived neurotrophic factor acutely enhances tyrosine phosphorylation of the AMPA receptor subunit GluR1 via NMDA receptor-dependent mechanisms. Brain Res Mol Brain Res 130:178–186PubMedCrossRefGoogle Scholar
  62. Yamada M, Ohnishi H, Sano S, Araki T, Nakatani A, Ikeuchi T, Hatanaka H (1999) Brain-derived neurotrophic factor stimulates interactions of Shp2 with phosphatidylinositol 3-kinase and Grb2 in cultured cerebral cortical neurons. J Neurochem 73:41–49PubMedCrossRefGoogle Scholar
  63. Yamada M, Tanabe K, Wada K, Shimoke K, Ishikawa Y, Ikeuchi T, Koizumi S, Hatanaka H (2001) Differences in survival-promoting effects and intracellular signaling properties of BDNF and IGF-1 in cultured cerebral cortical neurons. J Neurochem 78:940–951PubMedCrossRefGoogle Scholar
  64. Yamada M, Numakawa T, Koshimizu H, Tanabe K, Wada K, Koizumi S, Hatanaka H (2002) Distinct usages of phospholipase C gamma and Shc in intracellular signaling stimulated by neurotrophins. Brain Res 955:183–190PubMedCrossRefGoogle Scholar
  65. Yeiser EC, Rutkoski NJ, Naito A, Inoue J, Carter BD (2004) Neurotrophin signaling through the p75 receptor is deficient in traf6-/- mice. J Neurosci 24:10521–10529PubMedCrossRefGoogle Scholar
  66. Yin YX, Sun ZP, Huang SH, Zhao L, Geng Z, Chen ZY (2010) RanBPM contributes to TrkB signaling and regulates brain-derived neurotrophic factor-induced neuronal morphogenesis and survival. J Neurochem 114:110–121PubMedGoogle Scholar
  67. Zhang S, Guo D, Luo W, Zhang Q, Zhang Y, Li C, Lu Y, Cui Z, Qiu X (2010) TrkB is highly expressed in NSCLC and mediates BDNF-induced the activation of Pyk2 signaling and the invasion of A549 cells. BMC Cancer 10:43PubMedCentralPubMedCrossRefGoogle Scholar
  68. Zhao CT, Li K, Li JT, Zheng W, Liang XJ, Geng AQ, Li N, Yuan XB (2009) PKCdelta regulates cortical radial migration by stabilizing the Cdk5 activator p35. Proc Natl Acad Sci U S A 106:21353–21358PubMedCentralPubMedCrossRefGoogle Scholar
  69. Zuccato C, Ciammola A, Rigamonti D, Leavitt BR, Goffredo D, Conti L, MacDonald ME, Friedlander RM, Silani V et al (2001) Loss of huntingtin-mediated BDNF gene transcription in Huntington’s disease. Science 293:493–498PubMedCrossRefGoogle Scholar

Copyright information

© The International CCN Society 2013

Authors and Affiliations

  • Varot K. Sandhya
    • 1
  • Rajesh Raju
    • 1
  • Renu Verma
    • 1
    • 2
  • Jayshree Advani
    • 1
  • Rakesh Sharma
    • 1
    • 3
  • Aneesha Radhakrishnan
    • 1
    • 4
  • Vishalakshi Nanjappa
    • 1
    • 5
  • Jayasuryan Narayana
    • 2
  • B. L. Somani
    • 1
  • Kanchan K. Mukherjee
    • 6
  • Akhilesh Pandey
    • 7
  • Rita Christopher
    • 3
  • T. S. Keshava Prasad
    • 1
    • 5
  1. 1.Institute of BioinformaticsInternational Tech ParkBangaloreIndia
  2. 2.Microtest Innovations Pvt. Ltd.BangaloreIndia
  3. 3.Department of NeurochemistryNational Institute of Mental health and NeurosciencesBangaloreIndia
  4. 4.Department of Biochemistry and Molecular BiologyPondicherry UniversityPuducherryIndia
  5. 5.Amrita School of BiotechnologyAmrita Vishwa VidyapeethamKollamIndia
  6. 6.Department of NeurosurgeryPostgraduate Institute of Medical Education & ResearchChandigarhIndia
  7. 7.McKusick-Nathans Institute of Genetic Medicine and Departments of Biological Chemistry, Pathology and OncologyJohns Hopkins University School of MedicineBaltimoreUSA

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