Tyrosine phosphorylation of 3BP2 is indispensable for the interaction with VAV3 in chicken DT40 cells

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• 作者：Kazuyasu Chihara ; Yukihiro Kimura ; Chisato Honjoh ; Shota Yamauchi ; Kenji Takeuchi ; Kiyonao Sada
• 关键词：3BP2 ; c-Abl SH3 domain-binding protein-2 ; SH2 ; Src homology 2 ; BCR ; B cell receptor ; NFAT ; nuclear factor of activated T cells ; PLC ; phospholipase C ; SH3 ; Src homology 3 ; mAb ; monoclonal antibody ; BLNK ; B cell linker protein
• 刊名：Experimental Cell Research
• 出版年：10 March, 2014
• 年：2014
• 卷：322
• 期：1
• 页码：99-107
• 全文大小：1107 K

文摘

Adaptor protein c-Abl SH3 domain-binding protein-2 (3BP2) is known to play regulatory roles in immunoreceptor-mediated signal transduction. We have previously demonstrated that Tyr¹⁷⁴, Tyr¹⁸³ and Tyr⁴⁴⁶ in mouse 3BP2 are predominantly phosphorylated by Syk, and the phosphorylation of Tyr¹⁸³ and the Src homology 2 (SH2) domain of mouse 3BP2 are critical for B cell receptor (BCR)-induced activation of nuclear factor of activated T cells (NFAT) in human B cells. In this report, we have shown that Syk, but not Abl family protein-tyrosine kinases, is critical for BCR-mediated tyrosine phosphorylation of 3BP2 in chicken DT40 cells. Mutational analysis showed that Tyr¹⁷⁴, Tyr¹⁸³ and Tyr⁴²⁶ of chicken 3BP2 are the major phosphorylation sites by Syk and the SH2 domain of 3BP2 is critical for tyrosine phosphorylation. In addition, phosphorylation of Tyr⁴²⁶ is required for the inducible interaction with the SH2 domain of Vav3. Moreover, the expression of the mutant form of 3BP2 in which Tyr⁴²⁶ was substituted to Phe resulted in the reduction in BCR-mediated Rac1 activation, when compared with the case of wild-type. Altogether, these data suggest that 3BP2 is involved in the activation of Rac1 through the regulation of Vav3 by Syk-dependent phosphorylation of Tyr⁴²⁶ following BCR stimulation.