Phosphatidylinositol (PtdIns) (3) kinase phosphorylates the D-3 position of the inositolring of PtdIns, producing PtdIns(3)P, PtdIns(3,4)P2, and PtdIns(3,4,5)P3. PI3-kinase is a heterodimer of an 85 kDa regulatory subunit (p85) and a 110 kDa catalytic subunit (p110). However, it is only one member of a larger family of proteins with similarity to the p110 subunit. These different PI3-kinase isoforms have been divided into three classes. Class I consists of p110alpha and p110ß which bind the p85 subunit and associate with receptor tyrosine kinases. Class II includes 68D and cpk from Drosophila, p170 and cpk-m from mouse, and C2alpha, C2ß (HsC2), and C2gamma from human. These proteins phosphorylate PtdIns and PtdIns(4)P, but not PtdIns(4,5)P2, and each contain a C-terminal C2 domain that may negatively regulate the catalytic domain. Class III members only phosphorylate PtdIns to PtdIns(3)P and include the S. cerevisiae Vps34p and its human homologs. In humans, the class II PI3-kinases C2alpha and C2ß have similar catalytic, PI kinase, and C2 domains. However they differ in their N-terminal regions. In addition, C2ß has no cation specificity, while C2alpha prefers Mg2+-ATP for optimal phosphorylation.