SHC1 binds phosphorylated ERBB2 heterodimers

Stable Identifier
Reaction [binding]
Homo sapiens
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SHC1 binds phosphorylated ERBB2:EGFR heterodimers through phosphorylated tyrosine residues on either ERBB2 (Y1196, Y1221, Y1222 and Y1248) or EGFR (Y1148 and Y1173) (Pinkas-Kramarski et al. 1996). Heterodimers of ERBB2 and ERBB3 recruit SHC1 through a phosphorylated tyrosine residue Y1328 in the C-tail of ERBB3 (Pinkas-Kramarski et al. 1996). Heterodimers of ERBB2 and ERBB4 isoforms recruit SHC1 through phosphorylated tyrosines in the C-tail of either ERBB2 (Y1196, Y1221, Y1222 and Y1248) or ERBB4 (Y1188 and Y1242 in ERBB4 JM-A CYT1 isoform; Y1178 and Y1232 in ERBB4 JM-B CYT1 isoform; Y1172 and Y1226 in ERBB4 JM-A CYT2 isoform) (Cohen et al. 1996, Kaushansky et al. 2008). Association of SHC1 with ERBB2:EGFR and ERBB2:ERBB3 heterodimers was demonstrated in engineered mouse 32D cells in which human ERBB2, EGFR and ERBB3 were expressed. Therefore, these experiments showed association of human ERBB receptor dimers and mouse Shc1. In the case of ERBB2:ERBB4 heterodimers, direct evidence, involving human proteins only, is available.

Binding of SHC1 to activated ERBB2 and the consequent RAS signaling activation is inhibited by the action of the PTPN12 protein tyrosine phosphatase. PTPN12 dephosphorylates tyrosine residue Y1248 of activated ERBB2 which serves as one of the docking sites for SHC1 in the ERBB2 C-terminus (Sun et al. 2011).

Literature References
PubMed ID Title Journal Year
8665853 Diversification of Neu differentiation factor and epidermal growth factor signaling by combinatorial receptor interactions

Ratzkin, BJ, Klapper, L, Levkowitz, G, Seger, R, Alroy, I, Waterman, H, Sela, M, Yarden, Y, Lavi, S, Pinkas-Kramarski, R, Soussan, L

EMBO J 1996
21376233 Activation of multiple proto-oncogenic tyrosine kinases in breast cancer via loss of the PTPN12 phosphatase

Schmitt, E, Creighton, CJ, Hilsenbeck, SG, Gygi, SP, Bernardi, RJ, Osborne, CK, Westbrook, TF, Muzny, D, Kessler, JD, Shaw, CA, Pavlova, NN, Schiff, R, Hu, G, Sun, T, Elledge, SJ, Zhou, C, Bentires-Alj, M, Wheeler, DA, Dephoure, N, Huang, J, Li, MZ, Gibbs, RA, Rao, M, Nguyen, DX, Aceto, N, Meerbrey, KL, Migliaccio, I, Botero, M

Cell 2011
18721752 System-wide investigation of ErbB4 reveals 19 sites of Tyr phosphorylation that are unusually selective in their recruitment properties

Lane, WS, MacBeath, G, Budnik, BA, Rush, J, Kaushansky, A, Gordus, A

Chem Biol 2008
8617750 HER4-mediated biological and biochemical properties in NIH 3T3 cells. Evidence for HER1-HER4 heterodimers

Fell, HP, Foy, L, Green, JM, Cohen, BD

J Biol Chem 1996
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