Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 191, Issue 4, Pages 641-650Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.191.4.641
Keywords
adaptor molecule; antigen receptor; lymphocyte; negative regulator; signaling
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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)-gamma 2 activation, thereby leading to increased apoptosis. A possible explanation for the involvement of Cbl in PLC-gamma 2 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-gamma 2 tyrosine phosphorylation through its binding to the PLC-gamma 2 SH2 domains. As a consequence of the interaction between Cbl and BLNK, die BCR-induced recruitment of PLC-gamma 2 to BLNK and the subsequent PLC-gamma 2 tyrosine phosphorylation were inhibited. Thus, our data suggest that Cbl negatively regulates the PLC-gamma 2 pathway by inhibiting the association of PLC-gamma 2 with BLNK.
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