Original Article

Cbl Suppresses B Cell Receptor–mediated Phospholipase C (PLC)-2 Activation by Regulating B Cell Linker Protein–PLC-2 Binding

Correspondence to: Tomohiro Kurosaki, Dept. of Molecular Genetics, Institute for Liver Research, Kansai Medical University, Moriguchi 570-8506, Japan. Tel:81-6-6993-9445 Fax:81-6-6994-6099 E-mail:kurosaki{at}mxr.mesh.ne.jp.

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)-2 activation, thereby leading to increased apoptosis. A possible explanation for the involvement of Cbl in PLC-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-2 tyrosine phosphorylation through its binding to the PLC-2 SH2 domains. As a consequence of the interaction between Cbl and BLNK, the BCR-induced recruitment of PLC-2 to BLNK and the subsequent PLC-2 tyrosine phosphorylation were inhibited. Thus, our data suggest that Cbl negatively regulates the PLC-2 pathway by inhibiting the association of PLC-2 with BLNK.

Key Words: adaptor molecule, antigen receptor, lymphocyte, negative regulator, signaling

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