Trk receptor autophosphorylates

Stable Identifier
R-RNO-181812
Type
Reaction [transition]
Species
Rattus norvegicus
Compartment
ReviewStatus
5/5
General
SVG |   | PPTX  | SBGN
Trk receptor autophosphorylates
NGF binding induces a conformational change in TRKA, which entails the activation of the receptor kinase domain. TRK receptor activation results in phosphorylation of several of ten evolutionary conserved tyrosines present in the cytoplasmic domain of each receptor. Phosphorylation of the three tyrosines in the activation loop of the kinase domain (Y670, Y674, and Y675 in TRKA) enhances tyrosine kinase activity. Phosphorylation of TRKA Y490 and Y785 creates docking sites for proteins containing SH2 or PTB domains: Y490 is the docking site for SHC, FRS2 and IRS1/2, Y785 interacts with PLC-gamma-1. Three other tyrosine residues are important for signalling but it is not clear how. It is possible that they play a structural role in the receptor. Therefore, full activity of TRKA receptor requires eight tyrosine residues.
Human TRKA comes in two isoforms, named TRKA- I (790 a.a long) and TRKA- II (796 a.a. long). The tyrosine phosphorylation site numbering refers to TRKA- I. The site numbering in TRK-II is equal to TRK- I numbering + 6 (that is: Y490 in TRK- I corresponds to Y496 in TRK- II, and so on).The same modifications occur at the homologous sites of rat TrkA, which also comes in the two isoforms I and II.
Literature References
PubMed ID Title Journal Year
8155326 Trk receptors use redundant signal transduction pathways involving SHC and PLC-gamma 1 to mediate NGF responses

Pawson, T, Kaplan, DR, Greene, LA, Stephens, RM, Copeland, TD, Loeb, DM

Neuron 1994
9099755 Autophosphorylation of activation loop tyrosines regulates signaling by the TRK nerve growth factor receptor

Greene, LA, Kaplan, DR, Cunningham, ME, Stephens, RM

J Biol Chem 1997
Participants
Orthologous Events
Created
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