MEMBRANE-BOUND EZRIN IS INVOLVED IN B-CELL RECEPTOR-MEDIATED SIGNALING - POTENTIAL ROLE OF AN ITAM-LIKE EZRIN MOTIF

Ezrin is a cytoskeleton-plasma membrane linker molecule which is impli cated in the T-cell antigen receptor signaling as one of the major tyr osine phosphorylated components. Its function in B-lymphocyte activati on has not yet been clarified. Here we studied the potential involveme nt of ezrin in the B-cell receptor (BCR) signaling in BL41 Burkitt lym phoma cells. Our data demonstrate that ezrin, which shows predominantl y cytosolic distribution in unstimulated cells, undergoes only a moder ate tyrosine phosphorylation in response to BCR triggering, with no co ncomitant translocation of the protein from the cytosol to the plasma membrane. Instead, BCR-independent stimulants like oxidant stress indu ced by phenylarsine oxide, resulted in rapid redistribution of ezrin t o the plasma membrane. When BCR triggering was preceded by membrane re cruitment of ezrin, it became one of the main and earliest substrates of tyrosine kinases activated by BCR. No detectable influence on distr ibution or phosphorylation of ezrin was triggered by the tyrosine phos phatase inhibition by orthovanadate, suggesting that these effects of phenylarsine oxide are not attributable to its tyrosine phosphatase in hibitory capacity. The notion that BCR-mediated phosphorylation of ezr in negatively correlates with activation events such as phosphorylatio n of tyrosine kinase, syk and induction of calcium mobilization respon se, suggests that ezrin might be implicated in the regulation of trans membrane signaling and cellular responsiveness. As will be discussed, the regulatory function of ezrin may be due to an immunoreceptor tyros ine-based activation motif (ITAM)-like sequence. (C) 1996 Elsevier Sci ence B.V.