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PMID: 10684856 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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 ·2000-02-21 ·Pages 641-50

Yasuda T, Maeda A, Kurosaki M, Tezuka T, Hironaka K, Yamamoto T, Kurosaki T

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.

MeSH Terms
Adaptor Proteins, Signal Transducing Animals Apoptosis B-Lymphocytes/immunology Carrier Proteins/metabolism Chickens Enzyme Activation Genomic Library Humans Isoenzymes/genetics,metabolism Karyotyping Mutagenesis, Site-Directed Oncogene Protein v-cbl Phospholipase C gamma Phosphoproteins/metabolism Receptors, Antigen, B-Cell/immunology Recombinant Proteins/metabolism Retroviridae Proteins, Oncogenic/genetics,physiology Signal Transduction Type C Phospholipases/genetics,metabolism
Chemicals
Adaptor Proteins, Signal Transducing B cell linker protein Carrier Proteins Isoenzymes Oncogene Protein v-cbl Phosphoproteins Receptors, Antigen, B-Cell Recombinant Proteins Retroviridae Proteins, Oncogenic Type C Phospholipases Phospholipase C gamma
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Yasuda T
Department of Oncology, Institute of Medical Science, University of Tokyo, Tokyo 108-0071, Japan.
Maeda A
Kurosaki M
Tezuka T
Hironaka K
Yamamoto T
Kurosaki T
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.191.4.641
Published
2000-02-21
Pages
641-50
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2195830
Subset
IM
External Links
PubMed source DOI: 10.1084/jem.191.4.641 PMC Full Text View journal details
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