Phosphoinositide 3-kinase and its targets in B-cell and T-cell signaling

Abstract

Phosphoinositide 3-kinase (PI3K) activation is essential for lymphocyte proliferation driven by receptors for antigen, costimulatory ligands and cytokines. The lipid products of PI3K contribute to the assembly of membrane-associated signaling complexes by promoting recruitment of selected proteins from the cytoplasm. Many proteins possess domains that are able to bind selectively to PI3K products. Different 'PI3K effector' proteins are coupled to distinct biological responses, depending on cell type and on the receptor that is engaged. In B cells and T cells, Tec-family tyrosine kinases and Akt serine/threonine kinases are emerging as crucial mediators of proliferation and survival signals downstream of PI3K. Of particular interest is recent evidence that PI3K signaling controls increases in lymphocyte size and metabolic activity that accompany cell cycle progression.