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 implicated in the T-cell antigen receptor signaling as one of the major tyrosine phosphorylated components. Its function in B-lymphocyte activation has not yet been clarified. Here we studied the potential involvement of ezrin in the B-cell receptor (BCR) signaling in BL41 Burkitt lymphoma cells. Our data demonstrate that ezrin, which shows predominantly cytosolic distribution in unstimulated cells, undergoes only a moderate tyrosine phosphorylation in response to BCR triggering, with no concomitant translocation of the protein from the cytosol to the plasma membrane. Instead, BCR-independent stimulants like oxidant stress induced by phenylarsine oxide, resulted in rapid redistribution of ezrin to the plasma membrane. When BCR triggering was preceded by membrane recruitment of ezrin, it became one of the main and earliest substrates of tyrosine kinases activated by BCR. No detectable influence on distribution or phosphorylation of ezrin was triggered by the tyrosine phosphatase inhibition by orthovanadate, suggesting that these effects of phenylarsine oxide are not attributable to its tyrosine phosphatase inhibitory capacity. The notion that BCR-mediated phosphorylation of ezrin negatively correlates with activation events such as phosphorylation of tyrosine kinase, syk and induction of calcium mobilization response, suggests that ezrin might be implicated in the regulation of transmembrane signaling and cellular responsiveness. As will be discussed, the regulatory function of ezrin may be due to an immunoreceptor tyrosine-based activation motif (ITAM)-like sequence.
Rozsnyay
Z
Z
Department of Immunoregulation, Vienna International Research Cooperation Center at Sandoz Research Institute, Austria. z.rozsnyay@dkfz-heidelberg.ge
Sarmay
G
G
Zoller
M
M
Gergely
J
J
D000199:Actins / Q000276:immunology; D001665:Binding Sites; D002462:Cell Membrane; D003593:Cytoplasm; D003598:Cytoskeletal Proteins; D006801:Humans; D018384:Oxidative Stress / Q000276:immunology; D010750:Phosphoproteins / Q000276:immunology*; D010766:Phosphorylation; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000276:immunology; D000099149:Ezrin
D000199:Actins; D003598:Cytoskeletal Proteins; D010750:Phosphoproteins; D011947:Receptors, Antigen, B-Cell; D014443:Tyrosine; D000099149:Ezrin