PI3K events in ERBB2 signaling

ERBB2:ERBB3 and ERBB2:ERBB4cyt1 heterodimers activate PI3K signaling by direct binding of PI3K regulatory subunit p85 to phosphorylated tyrosine residues in the C-tail of ERBB3 (Y1054, Y1197, Y1222, Y1224, Y1276 and Y1289) and ERBB4 CYT1 isoforms (Y1056 in JM-A CYT1 isoform and Y1046 in JM-B CYT1 isoform). Regulatory subunit p85 subsequently recruits catalytic subunit p110 of PI3K, resulting in the formation of active PI3K, conversion of PIP2 to PIP3, and PIP3-mediated activation of AKT signaling. Heterodimers of ERBB2 and EGFR recruit PI3K indirectly, through GRB2:GAB1 complex, which again leads to PIP3-mediated activation of AKT signaling.

Summary from Reactome (R-HSA-1963642), read 2026-09-23.