Quantitative Phosphoproteomics Reveals SLP-76 Dependent Regulation of PAG and Src Family Kinases in T Cells

被引：22

作者：

Cao, Lulu ^{[1
]}

Ding, Yiyuan ^{[1
]}

Hung, Norris ^{[2
]}

Yu, Kebing ^{[1
]}

Ritz, Anna ^{[3
]}

Raphael, Benjamin J. ^{[3
]}

Salomon, Arthur R. ^{[1
,2
]}

机构：

[1] Brown Univ, Dept Chem, Providence, RI 02912 USA

[2] Brown Univ, Dept Mol Biol Cell Biol & Biochem, Providence, RI 02912 USA

[3] Brown Univ, Dept Comp Sci, Providence, RI 02912 USA

来源：

PLOS ONE | 2012年 / 7卷 / 10期

基金：

美国国家卫生研究院;

关键词：

PROTEIN-TYROSINE KINASES; TRANSMEMBRANE ADAPTER PROTEIN; N-TERMINAL REGION; MASS-SPECTROMETRY; PHOSPHOLIPASE C-GAMMA-1; PHOSPHORYLATION SITES; PHOSPHATIDYLINOSITOL; 3-KINASE; PHOSPHOTYROSINE PHOSPHATASE; INTERLEUKIN-2; PRODUCTION; ENRICHED MICRODOMAINS;

D O I：

10.1371/journal.pone.0046725

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

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, PLC gamma, 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.

引用

页数：15

共 87 条

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