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 (p85 alpha, p85 beta, p55 alpha, p50 alpha, or p55 gamma) and one 110-kDa catalytic subunit (p110 alpha, beta or delta). The Class IB PI 3-kinase is also a dimer, composed of one regulatory subunit (p101 or p87) and one catalytic subunit (p110 gamma) (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.