TrkA,
apparent molecular weight 140 kDa, is a high affinity nerve
growth factor (NGF). The Trk protoongogene 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, Tyr751 and
Tyr785) to activate multiple downstream effector proteins.
Phosphorylation at Tyr490 is required for Shc association
and subsequent activation of the Ras-MAP kinase-signaling
cascade, which leads to activation of Elk-1-dependent gene
transcription and neurite growth. Phosphorylations at Tyr674
and Tyr675 lie within the catalytic domain of TrkA tyrosine
kinase and reflect Trk kinase activity. Additionally, phosphorylation
at Tyr751 is required for PI3-kinase association and activation
of the Akt signaling cascade.
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