Regulation of the phospholipase C-γ2 pathway in B cells

Gene-targeting experiments in DT40 chicken B cells highlighted the importance of the intracellular protein tyrosine kinases Syk and Btk in phospholipase C (PLC)-gamma2 activation. Until recently, the molecular mechanism underlying the double requirement for Syk and Btk in PLC-gamma2 activation remained unclear, but new data suggest that an adaptor molecule, named BLNK, after being phosphorylated by Syk, provides docking sites for Btk SH2 domain as well as PLC-gamma2 SH2 domains, thus bringing Btk into close proximity with PLC-gamma2. The activated Btk then phosphorylates PLC-gamma2, leading to its activation. Inositol 1,4,5-trisphosphate OPA generated by PLC-gamma2 activation, binds to IP3 receptors, which is essential for triggering a calcium release from the endoplasmic reticulum (ER) and subsequent entry of extracellular calcium. (C) 2002 Elsevier Science B.V. All rights reserved.