The Adaptor Protein BLNK Is Required for B Cell Antigen Receptor-induced Activation of Nuclear Factor-κB and Cell Cycle Entry and Survival of B Lymphocytes

• DOI: 10.1074/jbc.m010800200
• Publication Date: 2002-07-26T15:09:24Z
• Authors: Joy En-Lin Tan; Siew-Cheng Wong; Samuel Ken-En Gan; Shengli Xu; Kong-Peng Lam
• Keywords: 0301 basic medicine; B-Lymphocytes; Cell Survival; Phospholipase C gamma; Cell Cycle; NF-kappa B; Receptors, Antigen, B-Cell; Protein-Tyrosine Kinases; Lymphocyte Activation; Phosphoproteins; Enzyme Activation; Isoenzymes; 03 medical and health sciences; 0302 clinical medicine; Immunoglobulin M; Type C Phospholipases; Agammaglobulinaemia Tyrosine Kinase; Humans; Carrier Proteins; Adaptor Proteins, Signal Transducing

B lymphocytes lacking the adaptor protein cell linker (BLNK) do not proliferate in response to antigen receptor (BCR) engagement. We demonstrate here that BCR-activated BLNK(-)/- cells fail enter cycle, and this is due their inability induce expression of cycle regulatory proteins such as cyclin D2 cyclin-dependent kinase 4. BCR-stimulated also up-regulate survival Bcl-x(L), which may be necessary for complete cycle. In addition, exhibit a high rate spontaneous apoptosis culture. Examination various signaling pathways mouse reveals intact activation Akt mitogen-activated kinases but impaired nuclear factor (NF)-kappaB known regulate genes involved proliferation survival. The activate NF-kappaB failure degradation inhibitory kappaB protein. all these aspects, resemble xid have mutation Bruton's tyrosine (Btk). Recently, phospholipase C (PLC)-gamma2 has been demonstrated essential activation. Since BLNK shown separately interact with both Btk PLC-gamma2, our finding normal PLC-gamma2 strongly suggests orchestrates formation Btk-PLC-gamma2 axis regulates Taken together, defect sufficient explain similar defects BCR-induced T cell-independent immune responses BLNK(-)/-, Btk(-)/-, PLC-gamma2(-)/- mice.