ZAP-70 enhances B-cell–receptor signaling despite absent or inefficient tyrosine kinase activation in chronic lymphocytic leukemia and lymphoma B cells

摘要: Expression of ZAP-70 is an important negative prognostic factor in chronic lymphocytic leukemia (CLL). This protein tyrosine kinase a key mediator T-cell receptor (TCR) signaling and structurally homologous to Syk, which plays analogous role B-cell (BCR) signaling. Recent studies indicate that may participate BCR as well, but the mechanism action not completely understood. We have now compared antigen receptor-induced activation B cells T by analyzing phosphorylation critical regulatory residues. show BCR-mediated very inefficient CLL lymphoma negligible when Syk. Despite catalytic activation, ability recruit downstream molecules response stimulation appeared relatively preserved. Moreover, ectopic expression enhanced prolonged several mediators signaling, such ERK, Akt kinases, decreased rate ligand-mediated internalization. conclude quite distinct from its TCR likely mediated inhibition events terminate response.