Cbl Suppresses B Cell Receptor–Mediated Phospholipase C (Plc)-γ2 Activation by Regulating B Cell Linker Protein–Plc-γ2 Binding

• Published in: The Journal of experimental medicine Vol. 191; no. 4; pp. 641 - 650
• Main Authors: Yasuda, Tomoharu, Maeda, Akito, Kurosaki, Mari, Tezuka, Tohru, Hironaka, Katsunori, Yamamoto, Tadashi, Kurosaki, Tomohiro
• Format: Journal Article
• Language: English
• Published: The Rockefeller University Press 21.02.2000
• Subjects: Original
• ISSN: 0022-1007; 1540-9538
• DOI: 10.1084/jem.191.4.641

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)-γ2 activation, thereby leading to increased apoptosis. A possible explanation for the involvement of Cbl in PLC-γ2 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-γ2 tyrosine phosphorylation through its binding to the PLC-γ2 SH2 domains. As a consequence of the interaction between Cbl and BLNK, the BCR-induced recruitment of PLC-γ2 to BLNK and the subsequent PLC-γ2 tyrosine phosphorylation were inhibited. Thus, our data suggest that Cbl negatively regulates the PLC-γ2 pathway by inhibiting the association of PLC-γ2 with BLNK.