Quantitative phosphoproteomics reveals SLP-76 dependent regulation of PAG and Src family kinases in T cells

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 downstr...

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Published in:PloS one 2012-10, Vol.7 (10), p.e46725
Main Authors: Cao, Lulu, Ding, Yiyuan, Hung, Norris, Yu, Kebing, Ritz, Anna, Raphael, Benjamin J, Salomon, Arthur R
Format: Article
Language:English
Subjects:
1-Phosphatidylinositol 3-kinase
Adapter proteins
Adaptor Proteins, Signal Transducing - genetics
Adaptor Proteins, Signal Transducing - metabolism
Amino Acid Motifs
Biochemistry
Biology
Cell adhesion & migration
Cell Line
Computer science
Cytokines
Extracellular signal-regulated kinase
Fyn protein
Humans
Intracellular Signaling Peptides and Proteins - metabolism
Itk protein
Kinases
Kinetics
Labeling
Lck protein
Leukocytes
Lymphocytes
Lymphocytes T
Membrane Proteins - metabolism
Molecular biology
Mutagenesis
Negative feedback
Peptides
Phosphatase
Phosphoproteins - genetics
Phosphoproteins - metabolism
Phosphorylation
Phosphotransferases
Protein Processing, Post-Translational
Proteomics
Receptors, Antigen, T-Cell - metabolism
Regulations
Scaffolding
Signal Transduction
Signaling
Site-directed mutagenesis
SLP-76 protein
Src protein
src-Family Kinases - metabolism
T cell receptors
T cells
T-cell receptor
T-Lymphocytes - metabolism
Tyrosine
White blood cells
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container_issue 10
container_start_page e46725
container_title PloS one
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creator Cao, Lulu
Ding, Yiyuan
Hung, Norris
Yu, Kebing
Ritz, Anna
Raphael, Benjamin J
Salomon, Arthur R
description 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.
doi_str_mv 10.1371/journal.pone.0046725
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subjects 1-Phosphatidylinositol 3-kinase
Adapter proteins
Adaptor Proteins, Signal Transducing - genetics
Adaptor Proteins, Signal Transducing - metabolism
Amino Acid Motifs
Biochemistry
Biology
Cell adhesion & migration
Cell Line
Computer science
Cytokines
Extracellular signal-regulated kinase
Fyn protein
Humans
Intracellular Signaling Peptides and Proteins - metabolism
Itk protein
Kinases
Kinetics
Labeling
Lck protein
Leukocytes
Lymphocytes
Lymphocytes T
Membrane Proteins - metabolism
Molecular biology
Mutagenesis
Negative feedback
Peptides
Phosphatase
Phosphoproteins - genetics
Phosphoproteins - metabolism
Phosphorylation
Phosphotransferases
Protein Processing, Post-Translational
Proteomics
Receptors, Antigen, T-Cell - metabolism
Regulations
Scaffolding
Signal Transduction
Signaling
Site-directed mutagenesis
SLP-76 protein
Src protein
src-Family Kinases - metabolism
T cell receptors
T cells
T-cell receptor
T-Lymphocytes - metabolism
Tyrosine
White blood cells
title Quantitative phosphoproteomics reveals SLP-76 dependent regulation of PAG and Src family kinases in T cells
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