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Details on Person SHC1 binds phosphorylated ERBB2:EGFR heterodimers through ph...

Class:IdSummation:1963574
_displayNameSHC1 binds phosphorylated ERBB2:EGFR heterodimers through ph...
_timestamp2019-08-07 18:14:14
created[InstanceEdit:1963565] Orlic-Milacic, M, 2011-11-03
modified[InstanceEdit:1977293] Orlic-Milacic, M, 2011-11-07
[InstanceEdit:8864026] Orlic-Milacic, Marija, 2016-03-10
[InstanceEdit:9655804] Orlic-Milacic, Marija, 2019-07-26
[InstanceEdit:9655806] Orlic-Milacic, Marija, 2019-07-26
[InstanceEdit:9657070] Orlic-Milacic, Marija, 2019-08-07
textSHC1 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).

(summation)[Reaction:1963578] SHC1 binds phosphorylated ERBB2 heterodimers [Homo sapiens]
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