原创力文档quantitative phosphoproteomics reveals slp-76 dependent regulation of pag and src family kinases in t cells定量phosphoproteomics揭示了slp - 76依赖pag的监管和src家族在t细胞激酶.pdfVIP
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quantitative phosphoproteomics reveals slp-76 dependent regulation of pag and src family kinases in t cells定量phosphoproteomics揭示了slp - 76依赖pag的监管和src家族在t细胞激酶
Quantitative Phosphoproteomics Reveals SLP-76
Dependent Regulation of PAG and Src Family Kinases in
T Cells
1 1 2 1 3 3
Lulu Cao , Yiyuan Ding , Norris Hung , Kebing Yu , Anna Ritz , Benjamin J. Raphael ,
Arthur R. Salomon1,2*
1 Department of Chemistry, Brown University, Providence, Rhode Island, United States of America, 2 Department of Molecular Biology, Cell Biology, and Biochemistry,
Brown University, Providence, Rhode Island, United States of America, 3 Department of Computer Science, Brown University, Providence, Rhode Island, United States of
America
Abstract
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, PLCc, 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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