Human PI3Ka is composed of two subunits: the catalytic subunit p110a, and a regulatory subunit,
p85a . After cell stimulation, PI3Ka is recruited to the membrane and activated by
binding, through an SH2 domain (nSH2) of p85, to phosphotyrosine motifs of activated membrane
receptors or their phosphorylated substrates. In vitro, phosphorylated peptides carrying the cognate
sequences (pY-pep) also activate the enzyme. The PIP3 lipids produced by activated PI3Ks act as
membrane docking sites for pleckstrin homology domain (PH)-containing proteins such as the AKT
serine/threonine kinases (also known as protein kinase B, PKB) and the 3-phosphoinositide-dependent
protein kinase-1 (PDK1) . Through this activity, class I PI3Ks link
cell-surface receptors including epidermal growth factor receptor, insulin-like growth factor receptor,
and platelet growth factor receptor to signaling networks that control cell growth, proliferation,
survival, apoptosis, differentiation, motility, migration, and adhesion