Quantitative phosphoproteomics reveals SLP-76 dependent regulation of PAG and Src family kinases in T cells.
Quantitative phosphoproteomics reveals SLP-76 dependent regulation of PAG and Src family kinases in T cells.
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DOI：
10.1371/journal.pone.0046725
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Salomon AR
中科院分区：
文献类型：
--
作者：
Cao L;Ding Y;Hung N;Yu K;Ritz A;Raphael BJ;Salomon AR
含SH 2结构域的76 kDa白细胞蛋白（SLP-76）在T细胞受体（TCR）信号传导中起着关键的支架作用。SLP-76作为一种含有多个蛋白结合结构域的衔接蛋白，与许多信号分子相互作用，并将近端受体刺激与下游效应器连接起来。已经使用Jurkat人白血病T细胞系通过蛋白质破坏或定点诱变广泛研究了SLP-76在TCR信号传导中的功能。然而，仍然缺乏对SLP-76依赖性磷酸化事件的广泛表征。对一百多个酪氨酸磷酸化位点的定量分析揭示了对PAG、PI 3 K和WASP磷酸化的新调节模式，同时重新证实了之前建立的SLP-76对Itk、PLCγ和Erk磷酸化的调节。SLP-76的缺乏也扰乱了Src家族激酶（SFKs）Lck和Fyn的磷酸化，以及随后的大量SFK调节的信号分子。总之，我们的数据表明，SLP-76在T细胞中调节正反馈和负反馈途径的独特模式，再次证实了其在该途径中的核心作用。
The SH2-domain-containing leukocyte protein of 76 kDa (SLP-76) plays a critical scaffolding role in T cell receptor (TCR) signaling. As an adaptor protein that contains multiple protein-binding domains, SLP-76 interacts with many signaling molecules and links proximal receptor stimulation to downstream effectors. The function of SLP-76 in TCR signaling has been widely studied using the Jurkat human leukaemic T cell line through protein disruption or site-directed mutagenesis. However, a wide-scale characterization of SLP-76-dependant phosphorylation events is still lacking. Quantitative profiling of over a hundred tyrosine phosphorylation sites revealed new modes of regulation of phosphorylation of PAG, PI3K, and WASP while reconfirming previously established regulation of Itk, PLCγ, and Erk phosphorylation by SLP-76. The absence of SLP-76 also perturbed the phosphorylation of Src family kinases (SFKs) Lck and Fyn, and subsequently a large number of SFK-regulated signaling molecules. Altogether our data suggests unique modes of regulation of positive and negative feedback pathways in T cells by SLP-76, reconfirming its central role in the pathway.
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DOI：
10.1084/jem.20030976
发表时间：
2004-01-05
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Badour K;Zhang J;Shi F;Leng Y;Collins M;Siminovitch KA
通讯作者：
Siminovitch KA
影响因子：
4.8
作者：
Beach, Dvora;Gonen, Ronnie;Yablonski, Deborah
通讯作者：
Yablonski, Deborah
影响因子：
5.4
作者：
Falco, M;Marcenaro, E;Bottino, C
通讯作者：
Bottino, C
影响因子：
4.8
作者：
Heyeck, SD;Wilcox, HM;Berg, LJ
通讯作者：
Berg, LJ
影响因子：
4.8
作者：
Bottini, N;Stefanini, L;Mustelin, T
通讯作者：
Mustelin, T