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- a nd heterotrimeric G-protein-linked receptors. We report herein the clo ning and charcterization of p110 delta, a novel class I PI3K, Like p11 0 alpha and p110 beta, other class I PI3Ks, p110 delta displays a broa d 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 si milarly recruited to activated signaling complexes after treatment wit h 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 ad aptor selection or recruitment to activated receptor complexes, Howeve r distinct biochemical and structural features of p1106 suggest diverg ent functional/regulatory capacities for this PI3K. Unlike p110 alpha, p1106 does not phosphorylate p85 but instead harbors an intrinsic aut ophosphorylation capacity, In addition, the p1106 catalytic domain con tains unique potential protein-protein interaction modules such as a P ro-rich region and a basic-region leucine-zipper (bZIP)-like domain, P ossible selective functions of p1106 in white blood cells are discusse d.