PXD005165

PXD005165 is an original dataset announced via ProteomeXchange.

Title	PLC-γ1 Can Regulate T-Cell Activation by Positive and Negative Feedback via Lck
Description	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.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:33:16.142.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Judson Belmont
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2016-10-17 02:05:09	ID requested
1	2017-06-27 23:35:34	announced
⏵ 2	2024-10-22 04:33:22	announced	2024-10-22: Updated project metadata.

10.1021/acs.jproteome.6b01026;

Belmont J, Gu T, Mudd A, Salomon AR, 1 Feedback Pathway Regulates Lck Substrate Phosphorylation at the T-Cell Receptor and SLP-76 Complex. J Proteome Res, 16(8):2729-2742(2017) [pubmed]

curator keyword: Biological

submitter keyword: Phosphoproteomics, Phospholipase C, TCR signaling, PLC-γ1,LC-MSMS

Art Salomon
contact affiliation	PI
contact email	art@drsalomon.com
lab head
Judson Belmont
contact affiliation	Brown University
contact email	Judson_Belmont@Brown.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD005165
     1. Label: PRIDE project
     2. Name: PLC-γ1 Can Regulate T-Cell Activation by Positive and Negative Feedback via Lck