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Cbl suppresses B cell receptor-mediated phospholipase C (PLC)-gamma2 activation by regulating B cell linker protein-PLC-gamma2 binding.
J Exp Med. 2000 Feb 21; 191(4):641-50.JE

Abstract

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.

Authors+Show Affiliations

Department of Oncology, Institute of Medical Science, University of Tokyo, Tokyo 108-0071, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

10684856

Citation

Yasuda, T, et al. "Cbl Suppresses B Cell Receptor-mediated Phospholipase C (PLC)-gamma2 Activation By Regulating B Cell Linker protein-PLC-gamma2 Binding." The Journal of Experimental Medicine, vol. 191, no. 4, 2000, pp. 641-50.
Yasuda T, Maeda A, Kurosaki M, et al. Cbl suppresses B cell receptor-mediated phospholipase C (PLC)-gamma2 activation by regulating B cell linker protein-PLC-gamma2 binding. J Exp Med. 2000;191(4):641-50.
Yasuda, T., Maeda, A., Kurosaki, M., Tezuka, T., Hironaka, K., Yamamoto, T., & Kurosaki, T. (2000). Cbl suppresses B cell receptor-mediated phospholipase C (PLC)-gamma2 activation by regulating B cell linker protein-PLC-gamma2 binding. The Journal of Experimental Medicine, 191(4), 641-50.
Yasuda T, et al. Cbl Suppresses B Cell Receptor-mediated Phospholipase C (PLC)-gamma2 Activation By Regulating B Cell Linker protein-PLC-gamma2 Binding. J Exp Med. 2000 Feb 21;191(4):641-50. PubMed PMID: 10684856.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cbl suppresses B cell receptor-mediated phospholipase C (PLC)-gamma2 activation by regulating B cell linker protein-PLC-gamma2 binding. AU - Yasuda,T, AU - Maeda,A, AU - Kurosaki,M, AU - Tezuka,T, AU - Hironaka,K, AU - Yamamoto,T, AU - Kurosaki,T, PY - 2000/2/24/pubmed PY - 2000/4/25/medline PY - 2000/2/24/entrez SP - 641 EP - 50 JF - The Journal of experimental medicine JO - J Exp Med VL - 191 IS - 4 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)-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. SN - 0022-1007 UR - https://www.unboundmedicine.com/medline/citation/10684856/Cbl_suppresses_B_cell_receptor_mediated_phospholipase_C__PLC__gamma2_activation_by_regulating_B_cell_linker_protein_PLC_gamma2_binding_ L2 - https://rupress.org/jem/article-lookup/doi/10.1084/jem.191.4.641 DB - PRIME DP - Unbound Medicine ER -