PIP3 activates AKT signaling PathwayStep5339 PathwayStep5343 PathwayStep5344 PathwayStep5345 PathwayStep5346 PathwayStep5340 PathwayStep5341 PathwayStep5342 PathwayStep5348 PathwayStep5347 Recruitment of catalytic PI3K subunit p110 (PIK3CA) by PIK3R1 bound to GRB2:GAB1 in complex with phosphorylated heterodimer of ERBB2 and EGFR Binding of PI3K subunit p85 (PIK3R1) to GRB2:GAB1 in complex with phosphorylated heterodimer of ERBB2 and EGFR. Binding of GRB2:GAB1 to p-ERBB2:p-EGFR PIP2 to PIP3 conversion by PI3K bound to phosphorylated heterodimer of ERBB2 and ERBB4 CYT1 PIP2 to PIP3 conversion by PI3K bound to GRB2:GAB1 in complex with phosphorylated heterodimer of ERBB2 and EGFR PIP2 to PIP3 conversion by PI3K bound to phosphorylated heterodimer of ERBB2 and ERBB3 Binding of p85 subunit of PI3K (PIK3R1) to p-ERBB2:p-ERBB4 CYT-1 heterodimers Recruitment of PI3K subunit p110 (PIK3CA) by PIK3R1bound to ERBB2:ERBB4cyt1 heterodimer. Recruitment of PI3K subunit p110 (PIK3CA) by PIK3R1 bound to phosphorylated heterodimer of ERBB2 and ERBB3. Binding of PI3K subunit p85 (PIK3R1) to ERBB2:P-ERBB3 heterodimer PI3K events in ERBB2 signaling Authored: Orlic-Milacic, M, 2011-11-04 ERBB2:ERBB3 and ERBB2:ERBB4cyt1 heterodimers activate PI3K signaling by direct binding of PI3K regulatory subunit p85 (Yang et al. 2007, Cohen et al. 1996, Kaushansky et al. 2008) 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 (Junttila et al. 2009, Kainulainen et al. 2000). Heterodimers of ERBB2 and EGFR recruit PI3K indirectly, through GRB2:GAB1 complex (Jackson et al. 2004), which again leads to PIP3-mediated activation of AKT signaling. Edited: D'Eustachio, P, 2011-11-07 Edited: Matthews, L, 2011-11-07 Reactome Database ID Release 431963642 Reactome, http://www.reactome.org ReactomeREACT_116008 Reviewed: Neckers, LM, 2011-11-11 Reviewed: Xu, W, 2011-11-11 PathwayStep3897