Find NTRK1 Products Interaction Network for NTRK1 NTRK1 Details

Related Pathways Neurotrophin / TRK Signaling Huntington's Disease Signaling Axonal Guidance Signaling View All Pathways

Synonyms: C80751, DKFZp781I14186, gp140trk, MTC, NTRK1, p140 TRK, p140-TrkA, PROTO-TRKA, Tkr, TRK, TRK1, TRKA, TRKA NGFR

TRKA Signaling

Neurotrophic tyrosine kinase receptor type 1 (TrkA), is the high affinity receptor for nerve growth factor (NGF). Activation of TrkA by NGF promotes survival, growth (mitosis) and/or differentiation of specific neuronal cell populations including sympathetic neurons, neural crest-derived sensory neurons, and basal forebrain cholinergic neurons. Specific cell responses to NGF-dependent TrkA-activation depend upon the balance of associated adaptor and kinase proteins and cell context.

TrkA activation typically leads to the activation of survival and growth mediating pathways through cytoplasmic proteins SHC; PI3-kinase and PLCgamma1. PI3-kinase activates the PDK-1/AKT(PKB) pathway that supports cell survival and protein synthesis. SHC provides a docking site for GRB2/SOS activation of the Ras/Raf/MEK/ERK growth promoting pathway and PLCgamma1 supports activation of the PKC pathway. While withdrawal of NGF leads to apoptosis, over expression of TrKA may also induce a switch from an ERK/CREB-dependent anti-apoptotic to a MEK3/6-p38MAP-dependent pro-apoptotic condition. PLC-gamma1 activity is involved in switching between anti-mitogenic and mitogenic signaling.

NGF-activated TrkA can promote cell growth (proliferation) or differentiation (neurite out-growth) of neurons depending on cell context. SHC regulates proliferation and Suc1-associated neurotrophic factor-induced tyrosine phosphorylation target (SNT-1)/fibroblast growth factor receptor substrate 1 (FRS-2) regulates differentiation. SHC and SNT-1/FRS-2 compete for the same site on TrkA. FRS-2 binds Grb-2, Crk, Sh-PTP-2, cyclin-dependent kinase substate (suc1) and Src. These factors link TrkA to the cell cycle. NGF activated TrkA can regulate development of the axonal cytoskeleton structures through a pathway that involves the non-receptor tyrosine kinase, c-Abl, c-Crk adaptor proteins and paxillin. Crk adaptor proteins are involved in the regulation of proliferation, anchorage-dependent DNA synthesis and cytoskeletal reorganization.