Reactome: EGFR autophosphorylation

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EGFR autophosphorylation
Stable identifier	REACT_9388.1
Authored	Castagnoli, L, 2006-10-10
Reviewed	Muthuswamy, S, 2007-02-16
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The cytoplasmic domain of EGFR contains tyrosine, serine and threonine phosphorylation sites. Dimerization of EGFR activates its intrinsic protein kinase activity and results in autophosphorylation of 5 of these sites (Y992, Y1068, Y1086, Y1148 and Y1173). Tyrosine autophosphorylation is crucial for normal receptor signalling as it provides specific binding sites for cytosolic target proteins involved in signal transmission.

Input (present at start of reaction)	EGF:EGFR dimer [plasma membrane] ATP [cytosol] C C P x 10
Output (present at end of reaction)	EGF:Phospho-EGFR (Y992, Y1068, Y1086, Y1148, Y1173) dimer [plasma membrane] ADP [cytosol] C C P x 10
Catalyst	EGF:EGFR dimer [plasma membrane]
Essential catalyst component	EGFR [plasma membrane] U K E G B C d O O R R H H U R R P P P P P P P P P P P P D D
GO molecular function	protein tyrosine kinase activity GO
Preceding event(s)	EGFR dimerization [Homo sapiens]
Following event(s)	Shc binds to the phospho-receptor:ligand complex [Homo sapiens] Gab1:Grb2 binds to EGF:Phospho-EGFR [Homo sapiens] Gab1:Grb2:PI3K binds to EGF:Phospho-EGFR [Homo sapiens] Sos:Grb2 complex binds to EGF:EGFR complex [Homo sapiens]
Organism	Homo sapiens
Cellular compartment	plasma membrane GO
External identifier	IntAct:EBI-640874 IntAct:irefindex:Jpn2Rk9B+8qwozS6L8ewXtvGXjw(rigid) IntAct:EBI-1035794 IntAct:irefindex:Jpn2Rk9B+8qwozS6L8ewXtvGXjw(rigid) IntAct:EBI-1034411 IntAct:irefindex:Jpn2Rk9B+8qwozS6L8ewXtvGXjw(rigid)
Walton, GM, Chen, WS, Rosenfeld, MG, Gill, GN Analysis of deletions of the carboxyl terminus of the epidermal growth factor receptor reveals self-phosphorylation at tyrosine 992 and enhanced in vivo tyrosine phosphorylation of cell substrates 1990 J Biol Chem PubMed Margolis, BL, Lax, I, Kris, R, Dombalagian, M, Honegger, AM, Howk, R, Givol, D, Ullrich, A, Schlessinger, J All autophosphorylation sites of epidermal growth factor (EGF) receptor and HER2/neu are located in their carboxyl-terminal tails. Identification of a novel site in EGF receptor. 1989 J Biol Chem PubMed Helin, K, Beguinot, L Internalization and down-regulation of the human epidermal growth factor receptor are regulated by the carboxyl-terminal tyrosines 1991 J Biol Chem PubMed
Equivalent event(s) in other organism(s)	EGFR autophosphorylation [Canis familiaris] EGFR autophosphorylation [Mus musculus] EGFR autophosphorylation [Rattus norvegicus] EGFR autophosphorylation [Gallus gallus] EGFR autophosphorylation [Taeniopygia guttata] EGFR autophosphorylation [Xenopus tropicalis] EGFR autophosphorylation [Danio rerio]
Participating molecules
ADP [cytosol] C C P ATP [cytosol] C C P EGF [extracellular region] U K E G B C d O R H U R P P P P EGFR [plasma membrane] U K E G B C d O O R R H H U R R P P P P P P P P P P P P D D Phospho-EGFR [plasma membrane] U K E G B C d O O R R H H U R R P P P P P P P P P P P P D D

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