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TrkA Receptor
The Trk proto-oncogene family contains four members, TrkA, TrkB, TrkC, and TrkE which are variably expressed throughout the central and peripheral nervous systems. TrkA binds to nerve growth factor (NGF) and autophosphorylates on tyrosine residues (Tyr490, Tyr674, Tyr675 ,Tyr 751, and Tyr785) leading to activation of multiple downstream effector proteins. Phosphorylation at Tyr490 is required for Shc association and subsequent activation of the Ras-MAP kinase signaling cascade that leads to activation of Elk-1-dependent gene transcription and neurite growth. In addition to the Ras-MAP kinase cascade, Ras also activates RhoA, which in turn, inhibits p21CIP-induced growth arrest. Phosphorylations at Tyr674 and Tyr675 lie within the catalytic domain of TrkA tyrosine kinase. Additionally, phosphorylation at Tyr751 is required for PI3-kinase association and activation of the Akt signaling cascade.
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References:
Yoon, S.O., et al., A dominant role of the juxtamembrane region of the TrkA nerve growth factor receptor during neuronal cell differentiation. J. Biol. Chem., 272, 23231-23238 (1997).
Encinas, M., et al., Extracellular-regulated kinases and phosphatidylinositol 3-kinase are involved in brain-derived neurotrophic factor-mediated survival and neuritogenesis of the neuroblastoma cell line SH-SY5Y. J. Neurochem., 73,1409-1421 (1999).
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