TY - JOUR
T1 - Cbl suppresses B cell receptor-mediated phospholipase C (PLC)-γ2 activation by regulating B cell linker protein-PLC-γ2 binding
AU - Yasuda, Tomoharu
AU - Maeda, Akito
AU - Kurosaki, Mari
AU - Tezuka, Tohru
AU - Hironaka, Katsunori
AU - Yamamoto, Tadashi
AU - Kurosaki, Tomohiro
PY - 2000/2/21
Y1 - 2000/2/21
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0034695890&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034695890&partnerID=8YFLogxK
U2 - 10.1084/jem.191.4.641
DO - 10.1084/jem.191.4.641
M3 - Article
C2 - 10684856
AN - SCOPUS:0034695890
VL - 191
SP - 641
EP - 650
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
SN - 0022-1007
IS - 4
ER -