A novel link between integrins, transmembrane-4 superfamily proteins (CD63 and CD81), and phosphatidylinositol 4-kinase

Enzymatic and immunochemical assays show a phosphatidylinositol 4-kinase in novel and specific complexes with proteins (CD63 and CD81) of the transmembrane 4 superfamily (TM4SF) and an integrin (alpha(3) beta(1)). The size (55 kDa) and other properties of the phosphatidylinositol 4-kinase (PI 4-K) (stimulated by nonionic detergent, inhibited by adenosine, inhibited by monoclonal antibody 4CG5) are consistent with PI 4-K type II. Not only was PI 4-K associated with alpha(3) beta(1)-CD63 complexes in alpha(3)-transfected K562 cells, but also it could be co-purified from CD63 in untransfected K562 cells lacking alpha(3) beta(1). Thus, TM4SF proteins may link PI 4-K activity to the alpha(3) beta(1) integrin. The alpha(5) beta(1) integrin, which does not associate with TM4SF proteins, was not associated with PI 4-K. Notably, alpha(3) beta(1)-CD63-CD81-PI 4-K complexes are located in focal complexes at the cell periphery rather than in focal adhesions. The novel linkage between integrins, transmembrane 4 proteins, and phosphoinositide signaling at the cell periphery may play a key role in cell motility and provides a signaling pathway distinct hom conventional integrin signaling through focal adhesion kinase.