STAP-2 is phosphorylated at tyrosine-250 by Brk and modulates Brk-mediated STAT3 activation
STAP-2 is phosphorylated at tyrosine-250 by Brk and modulates Brk-mediated STAT3 activation
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DOI：
10.1016/j.bbrc.2009.04.076
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发表时间：
2009-06-19
影响因子：
3.1
通讯作者：
Matsuda, Tadashi
中科院分区：
文献类型：
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作者：
Ikeda, Osamu;Miyasaka, Yuto;Matsuda, Tadashi
信号转导接头蛋白-2(STAP-2)是最近发现的一种接头蛋白，在其C-末端含有Pleckstrin和Src Homology 2(SH2)样结构域以及YXXQ基序。STAP-2又称乳腺肿瘤激酶(BRK)底物(BKS)。我们以前的研究表明，STAP-2与信号转导和转录激活因子3(STAT3)和STAT5结合，并调节信号转导和转录激活因子5(PAL)。它们下游的小路。在本研究中，我们利用一系列STAP-2 YF突变体和抗磷酸化的STAP-2 Tyr250抗体，确定STAP-2中的酪氨酸-250(Tyr250)是BRK磷酸化的主要位点。此外，STAP-2 Y250F突变蛋白的过表达影响了BRK介导的STAT3的激活。重要的是，小干扰RNA介导的内源性STAP-2表达的减少降低了BRK介导的STAT3的激活。综上所述，我们的研究结果表明，STAP-2被BRK在Tyr250处磷酸化，并在BRK介导的STAT3激活中发挥重要作用。(C)2009 Elsevier Inc.保留所有权利。
Signal transducing adaptor protein-2 (STAP-2) is a recently identified adaptor protein that contains Pleckstrin and Src homology 2 (SH2)-like domains as well as a YXXQ motif in its C-terminal region. STAP-2 is also known as breast tumor kinase (Brk) substrate (BKS). Our previous studies revealed that STAP-2 binds to signal transducer and activator of transcription 3 (STAT3) and STAT5, and regulates the signaling pal. path-ways downstream of them. In the present study, we identified tyrosine-250 (Tyr250) in STAP-2 as a major site of phosphorylation by Brk, using a series of STAP-2 YF mutants and anti-phospho-STAP-2 Tyr250 antibody. Furthermore, overexpression of the STAP-2 Y250F mutant protein affected Brk-mediated STAT3, activation. importantly, small-interfering RNA-mediated reduction of endogenous STAP-2 expression decreased Brk-mediated STAT3 activation. Taken together, our findings demonstrate that STAP-2 is phosphorylated at Tyr250 by Brk, and plays all important role in Brk-mediated STAT3 activation. (c) 2009 Elsevier Inc. All rights reserved.