BLNK mediates Syk-dependent Btk activation

Yoshihiro Baba, Shoji Hashimoto, Masato Matsushita, Dai Watanabe, Tadamitsu Kishimoto, Tomohiro Kurosaki, Satoshi Tsukada

Research output: Contribution to journalArticle

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Abstract

Btk is a critical molecule in B cell antigen receptor (BCR)-coupled signaling, and its activity is regulated by Lyn and Syk. Although the molecular mechanism of Lyn-dependent Btk activation has been investigated, that of Syk-dependent Btk activation has remained unidentified. We have demonstrated that BLNK mediates Syk-dependent Btk activation. In a reconstitution cell system, coexpression of BLNK allows Syk to phosphorylate Btk on its tyrosine 551, leading to the enhancement of Btk activity. This phosphorylation depends on the interaction of Btk and BLNK by means of the Btk-Src homology 2 domain. The existence of such an activation mechanism is supported by the observation that the BCR-induced Btk phosphorylation and activation are significantly reduced in BLNK-deficient B cells as well as in Syk-deficient B cells. Although previous observations have identified the function of BLNK as the linker that integrates the action of Btk and Syk into downstream effectors such as phospholipase Cγ2, our present study indicates another function of BLNK that connects the activity of Syk to that of Btk.

Original languageEnglish
Pages (from-to)2582-2586
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume98
Issue number5
DOIs
Publication statusPublished - Feb 27 2001
Externally publishedYes

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B-Cell Antigen Receptors
B-Lymphocytes
Phosphorylation
src Homology Domains
Phospholipases
Tyrosine

All Science Journal Classification (ASJC) codes

  • General

Cite this

Baba, Y., Hashimoto, S., Matsushita, M., Watanabe, D., Kishimoto, T., Kurosaki, T., & Tsukada, S. (2001). BLNK mediates Syk-dependent Btk activation. Proceedings of the National Academy of Sciences of the United States of America, 98(5), 2582-2586. https://doi.org/10.1073/pnas.051626198

BLNK mediates Syk-dependent Btk activation. / Baba, Yoshihiro; Hashimoto, Shoji; Matsushita, Masato; Watanabe, Dai; Kishimoto, Tadamitsu; Kurosaki, Tomohiro; Tsukada, Satoshi.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 98, No. 5, 27.02.2001, p. 2582-2586.

Research output: Contribution to journalArticle

Baba, Y, Hashimoto, S, Matsushita, M, Watanabe, D, Kishimoto, T, Kurosaki, T & Tsukada, S 2001, 'BLNK mediates Syk-dependent Btk activation', Proceedings of the National Academy of Sciences of the United States of America, vol. 98, no. 5, pp. 2582-2586. https://doi.org/10.1073/pnas.051626198
Baba, Yoshihiro ; Hashimoto, Shoji ; Matsushita, Masato ; Watanabe, Dai ; Kishimoto, Tadamitsu ; Kurosaki, Tomohiro ; Tsukada, Satoshi. / BLNK mediates Syk-dependent Btk activation. In: Proceedings of the National Academy of Sciences of the United States of America. 2001 ; Vol. 98, No. 5. pp. 2582-2586.
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