p110 delta, a novel phosphoinositide 3-kinase in leukocytes

Phosphoinositide 3-kinases (PI3Ks) are a family of lipid kinases that have been implicated in signal transduction through tyrosine kinase- and heterotrimeric G-protein-linked receptors. We report herein the cloning and charcterization of p110 delta, a novel class I PI3K, Like p110 alpha and p110 beta, other class I PI3Ks, p110 delta displays a broad phosphoinositide lipid substrate specificity and interacts with SH2/SH3 domain-containing p85 adaptor proteins and with GTP-bound Pas, In contrast to the widely distributed p110 alpha and beta, p110 delta is exclusively found in leukocytes. In these cells, p110 alpha and delta both associate with the p85 alpha and beta adaptor subunits and are similarly recruited to activated signaling complexes after treatment with the cytokines interleukin 3 and 4 and stem cell factor,Thus, , these class I PI3Ks appear not to be distinguishable at the level of p85 adaptor selection or recruitment to activated receptor complexes, However distinct biochemical and structural features of p1106 suggest divergent functional/regulatory capacities for this PI3K. Unlike p110 alpha, p1106 does not phosphorylate p85 but instead harbors an intrinsic autophosphorylation capacity, In addition, the p1106 catalytic domain contains unique potential protein-protein interaction modules such as a Pro-rich region and a basic-region leucine-zipper (bZIP)-like domain, Possible selective functions of p1106 in white blood cells are discussed.