Cbl suppresses B cell receptor-mediated phospholipase C (PLC)-gamma2 activation by regulating B cell linker protein-PLC-gamma2 binding.

Accumulating evidence indicates that the Cbl protein plays a negative role in immune receptor signaling; however, the mode of Cbl action in B cell receptor (BCR) signaling still remains unclear. DT40 B cells deficient in Cbl showed enhanced BCR-mediated phospholipase C (PLC)-gamma2 activation, thereby leading to increased apoptosis. A possible ...
explanation for the involvement of Cbl in PLC-gamma2 activation was provided by findings that Cbl interacts via its Src homology 2 (SH2) domain with B cell linker protein (BLNK) after BCR ligation. BLNK is a critical adaptor molecule for PLC-gamma2 tyrosine phosphorylation through its binding to the PLC-gamma2 SH2 domains. As a consequence of the interaction between Cbl and BLNK, the BCR-induced recruitment of PLC-gamma2 to BLNK and the subsequent PLC-gamma2 tyrosine phosphorylation were inhibited. Thus, our data suggest that Cbl negatively regulates the PLC-gamma2 pathway by inhibiting the association of PLC-gamma2 with BLNK.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Animals, Apoptosis, B-Lymphocytes, Carrier Proteins, Chickens, Enzyme Activation, Genomic Library, Humans, Isoenzymes, Karyotyping, Mutagenesis, Site-Directed, Oncogene Protein v-cbl, Phospholipase C gamma, Phosphoproteins, Receptors, Antigen, B-Cell, Recombinant Proteins, Retroviridae Proteins, Oncogenic, Signal Transduction, Type C Phospholipases
J. Exp. Med.
Date: Feb. 21, 2000
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