Figure 1. Physiological activation of class IA PI3K. The p110-p85 heterodimers, cytoplasmic in their basal state, dock to cellular membranes upon activation of various signal receptors, including receptor tyrosine kinases. A conformational change in p85 relieves the p110 catalytic site from inhibition by the p85 SH2 domains, and PtdIns(3,4,5)P₃ is generated. Akt (and others with pleckstin homology (PH) domains) bind to PtdIns(3,4,5)P₃ and build up local signaling platforms for multiple cellular pathways. SH3, Src-homology 3; BH, breakpoint-cluster region homology; nSH2, N-terminal Src-homology 2; iSH2, inter-SH2; cSH2, C-terminal Src-homology 2.