Phosphorylated p-6Y-ERBB2 heterodimers ERBB2 heterodimers Trans-autophosphorylation of ERBB2 heterodimers Authored: Orlic-Milacic, M, 2011-11-04 Dimers of ERBB2 and EGF-bound EGFR trans-autophosphorylate on six EGFR tyrosine residues and six ERBB2 tyrosine residues to form phosphorylated heterodimers that activate downstream signaling cascades (Ricci et al. 1995, Pinkas-Kramarski et al. 1996, Walton et al. 1990, Margolis et al. 1989, Hazan et al. 1990, Helin et al. 1991). <br><br> In heterodimers of ERBB2 and neuregulin-stimulated ERBB3, ERBB2 phosphorylates ERBB3 on tyrosine residues that serve as docking sites for p85 subunit of PI3K (Y1054, Y1197, Y1222, Y1224, Y1260, Y1276 and Y1289), as well as SHC1 (Y1328) and GRB7 (Y1199 and Y1262). Since ERBB3 lacks catalytic activity, it cannot phosphorylate ERBB2. Hovewer, since ERBB2:ERBB3 heterodimers usually oligomerize on the cell surface, ERBB2 can become trans-autophosphorylated by and adjacent ERBB2 protein. It is not known if ERBB2 in the ERBB2:ERBB3 hetero-oligomer is phosphorylated on all conserved tyrosine residues and if the phosphorylation status of ERBB2 in the ERBB2:ERBB3 hetero-oligoimer significantly affects signaling (Li et al. 2007, Pinkas-Kramarski et al. 1996, Prigent et al. 1994, Vijapurkar et al. 2003, Wallasch et al. 1995). <br><br> Heterodimers of ERBB2 and ERBB4 trans-autophosphorylate on tyrosine residues that serve as docking sites for PLC-gamma, GRB2 and SHC1, as well as p85 subunit of PI3K (PIK3R1) in the case of ERBB2 heterodimers with ERBB4 CYT1 isoforms (ERBB4cyt1) - ERBB4 JM-A CYT1 and ERBB4 JM-B-CYT1 (Li et al. 2007, Kaushansky et al. 2008, Hazan et al. 1990, Cohen et al. 1996). EC Number: 2.7.10 Edited: D'Eustachio, P, 2011-11-07 Edited: Matthews, L, 2011-11-07 Pubmed12651161 Pubmed1688559 Pubmed16978839 Pubmed1706616 Pubmed18721752 Pubmed2022652 Pubmed2543678 Pubmed7478576 Pubmed7556068 Pubmed8026468 Pubmed8617750 Pubmed8665853 Reactome Database ID Release 431963582 Reactome, http://www.reactome.org ReactomeREACT_116044 Reviewed: Neckers, LM, 2011-11-11 Reviewed: Xu, W, 2011-11-11 has a Stoichiometric coefficient of 43