Proteomics

Dataset Information

0

PLC-γ1 Can Regulate T-Cell Activation by Positive and Negative Feedback via Lck


ABSTRACT: Phospholipase C gamma 1 (PLC-γ1) occupies a critically important position in the T cell signaling pathway. While its functions as a regulator of both Ca2+ signaling and PKC-family kinases are well characterized, PLC-γ1’s role in the regulation of early T cell receptor signaling events is incomplete. Activation of the T cell receptor leads to the formation of a signalosome complex between SLP-76, LAT, PLC-γ1, Itk, and Vav1. Recent studies have revealed the existence of both positive and negative feedback pathways from components of the signalosome complex to the apical kinase in the pathway, Lck. To determine the role, if any, of PLC-γ1 in these feedback networks, we performed a quantitative phosphoproteomic analysis of the PLC-γ1-deficient T cells. These data revealed a previously unappreciated role for PLC-γ1 in the positive regulation of Zap-70 and T cell receptor tyrosine phosphorylation. Conversely, PLC-γ1 negatively regulated the phosphorylation of signalosome associated proteins including previously established Lck substrate phosphorylation sites within this complex. While the positive and negative regulatory phosphorylation sites on Lck were largely unchanged, Tyr192 phosphorylation was elevated in Jgamma1. The data supports a model wherein Lck’s targeting, but not its kinase activity is altered by PLC-γ1, possibly through Lck Tyr192 phosphorylation.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): T Cell, Cell Culture

DISEASE(S): Acute Leukemia

SUBMITTER: Judson Belmont  

LAB HEAD: Art Salomon

PROVIDER: PXD005165 | Pride | 2017-06-28

REPOSITORIES: pride

altmetric image

Publications

A PLC-γ1 Feedback Pathway Regulates Lck Substrate Phosphorylation at the T-Cell Receptor and SLP-76 Complex.

Belmont Judson J   Gu Tao T   Mudd Ashley A   Salomon Arthur R AR  

Journal of proteome research 20170706 8


Phospholipase C gamma 1 (PLC-γ1) occupies a critically important position in the T-cell signaling pathway. While its functions as a regulator of both Ca<sup>2+</sup> signaling and PKC-family kinases are well characterized, PLC-γ1's role in the regulation of early T-cell receptor signaling events is incompletely understood. Activation of the T-cell receptor leads to the formation of a signalosome complex between SLP-76, LAT, PLC-γ1, Itk, and Vav1. Recent studies have revealed the existence of bot  ...[more]

Similar Datasets

2016-05-31 | PXD002022 | Pride
2016-05-31 | PXD002023 | Pride
2015-01-07 | PXD001410 | Pride
2015-09-15 | E-MTAB-3242 | biostudies-arrayexpress
2020-11-12 | PXD020759 | Pride
2019-11-07 | PXD007086 | Pride
2018-10-19 | PXD009240 | Pride
2024-04-01 | GSE214990 | GEO
2015-09-29 | GSE73533 | GEO
2022-02-17 | PXD026335 | Pride