Cbl suppresses B cell receptor-mediated phospholipase C (PLC)-γ2 activation by regulating B cell linker protein-PLC-γ2 binding

Tomoharu Yasuda, Akito Maeda, Mari Kurosaki, Tohru Tezuka, Katsunori Hironaka, Tadashi Yamamoto, Tomohiro Kurosaki

Research output: Contribution to journalArticle

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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)-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.

Original languageEnglish
Pages (from-to)641-650
Number of pages10
JournalJournal of Experimental Medicine
Volume191
Issue number4
DOIs
Publication statusPublished - Feb 21 2000

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Type C Phospholipases
Protein C
B-Lymphocytes
src Homology Domains
Phosphorylation
B cell linker protein
Ligation
Apoptosis

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Cbl suppresses B cell receptor-mediated phospholipase C (PLC)-γ2 activation by regulating B cell linker protein-PLC-γ2 binding. / Yasuda, Tomoharu; Maeda, Akito; Kurosaki, Mari; Tezuka, Tohru; Hironaka, Katsunori; Yamamoto, Tadashi; Kurosaki, Tomohiro.

In: Journal of Experimental Medicine, Vol. 191, No. 4, 21.02.2000, p. 641-650.

Research output: Contribution to journalArticle

Yasuda, Tomoharu ; Maeda, Akito ; Kurosaki, Mari ; Tezuka, Tohru ; Hironaka, Katsunori ; Yamamoto, Tadashi ; Kurosaki, Tomohiro. / Cbl suppresses B cell receptor-mediated phospholipase C (PLC)-γ2 activation by regulating B cell linker protein-PLC-γ2 binding. In: Journal of Experimental Medicine. 2000 ; Vol. 191, No. 4. pp. 641-650.
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AU - Hironaka, Katsunori

AU - Yamamoto, Tadashi

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