p110δ , a Novel Phosphoinositide 3-Kinase in Leukocytes
Abstract
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 characterization of p110δ, a novel class I PI3K. Like p110α and p110β, other class I PI3Ks, p110δ displays a broad phosphoinositide lipid substrate specificity and interacts with SH2/SH3 domain-containing p85 adaptor proteins and with GTP-bound Ras. In contrast to the widely distributed p110α and β, p110δ is exclusively found in leukocytes. In these cells, p110α and δ both associate with the p85α and β 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 p110δ suggest divergent functional/regulatory capacities for this PI3K. Unlike p110α, p110δ does not phosphorylate p85 but instead harbors an intrinsic autophosphorylation capacity. In addition, the p110δ 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 p110δ in white blood cells are discussed.
- Publication:
-
Proceedings of the National Academy of Science
- Pub Date:
- April 1997
- DOI:
- 10.1073/pnas.94.9.4330
- Bibcode:
- 1997PNAS...94.4330V