The regulation of class IA PI 3-kinases by inter-subunit interactions

Phosphoinositide 3-kinases (PI 3-kinases) are activated by growth factor and hormone receptors, and regulate cell growth, survival, motility, and responses to changes in nutritional conditions (Engelman et al. 2006). PI 3-kinases have been classified according to their subunit composition and their substrate specificity for phosphoinositides (Vanhaesebroeck et al. 2001). The class IA PI 3-kinase is a heterodimer consisting of one regulatory subunit (p85α, p85β, p55α, p50α, or p55γ) and one 110-kDa catalytic subunit (p110a, b or d). The Class IB PI 3-kinase is also a dimer, composed of one regulatory subunit (p101 or p87) and one catalytic subunit (p110γ) (Wymann et al. 2003). Class I enzymes will utilize PI, PI[4]P, or PI[4,5]P2 as substrates in vitro, but are thought to primarily produce PI[3,4,5]P3 in cells.