Cbl-b positively regulates Btk-mediated activation of phospholipase C-γ2 in B cells

Tomoharu Yasuda, Tohru Tezuka, Akito Maeda, Tetsuya Inazu, Yuji Yamanashi, Hua Gu, Tomohiro Kurosaki, Tadashi Yamamoto

Research output: Contribution to journalArticle

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Abstract

Genetic studies have revealed that Cbl-b plays a negative role in the antigen receptor-mediated proliferation of lymphocytes. However, we show that Cbl-b-deficient DT40 B cells display reduced phospholipase C (PLC)-γ2 activation and Ca2+ mobilization upon B cell receptor (BCR) stimulation. In addition, the overexpression of Cbl-b in WEHI-231 mouse B cells resulted in the augmentation of BCR-induced Ca2+ mobilization. Cbl-b interacted with PLC-γ2 and helped the association of PLC-γ2 with Bruton's tyrosine kinase (Btk), as well as B cell linker protein (BLNK). Cbl-b was indispensable for Btk-dependent sustained increase in intracellular Ca2+. Both NH2-terminal tyrosine kinase-binding domain and COOH-terminal half region of Cbl-b were essential for its association with PLC-γ2 and the regulation of Ca2+ mobilization. These results demonstrate that Cbl-b positively regulates BCR-mediated Ca2+ signaling, most likely by influencing the Btk/BLNK/PLC-γ2 complex formation.

Original languageEnglish
Pages (from-to)51-63
Number of pages13
JournalJournal of Experimental Medicine
Volume196
Issue number1
DOIs
Publication statusPublished - Jul 1 2002

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Type C Phospholipases
B-Lymphocytes
Antigen Receptors
Protein-Tyrosine Kinases
Agammaglobulinaemia tyrosine kinase
Lymphocytes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Yasuda, T., Tezuka, T., Maeda, A., Inazu, T., Yamanashi, Y., Gu, H., ... Yamamoto, T. (2002). Cbl-b positively regulates Btk-mediated activation of phospholipase C-γ2 in B cells. Journal of Experimental Medicine, 196(1), 51-63. https://doi.org/10.1084/jem.20020068

Cbl-b positively regulates Btk-mediated activation of phospholipase C-γ2 in B cells. / Yasuda, Tomoharu; Tezuka, Tohru; Maeda, Akito; Inazu, Tetsuya; Yamanashi, Yuji; Gu, Hua; Kurosaki, Tomohiro; Yamamoto, Tadashi.

In: Journal of Experimental Medicine, Vol. 196, No. 1, 01.07.2002, p. 51-63.

Research output: Contribution to journalArticle

Yasuda, T, Tezuka, T, Maeda, A, Inazu, T, Yamanashi, Y, Gu, H, Kurosaki, T & Yamamoto, T 2002, 'Cbl-b positively regulates Btk-mediated activation of phospholipase C-γ2 in B cells', Journal of Experimental Medicine, vol. 196, no. 1, pp. 51-63. https://doi.org/10.1084/jem.20020068
Yasuda, Tomoharu ; Tezuka, Tohru ; Maeda, Akito ; Inazu, Tetsuya ; Yamanashi, Yuji ; Gu, Hua ; Kurosaki, Tomohiro ; Yamamoto, Tadashi. / Cbl-b positively regulates Btk-mediated activation of phospholipase C-γ2 in B cells. In: Journal of Experimental Medicine. 2002 ; Vol. 196, No. 1. pp. 51-63.
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