PXD002023

PXD002023 is an original dataset announced via ProteomeXchange.

Title	The catalytic activity of the kinase Zap-70 mediates basal signaling and negative feedback of the T cell receptor pathway
Description	T cell activation must be properly regulated to ensure normal T cell development and effective immune responses to pathogens and transformed cells, while avoiding autoimmunity. Our knowledge of the mechanisms controlling the fine-tuning of T cell receptor (TCR) signaling and T cell activation is still incomplete. The Syk family kinase ζ chain–associated protein kinase of 70 kD (ZAP-70) plays a critical role as part of the TCR signaling machinery that leads to T cell activation. To elucidate potential feedback targets that are dependent on the kinase activity of ZAP-70, we performed a mass spectrometry–based phosphoproteomic study to quantify temporal changes in phosphorylation patterns after inhibition of ZAP-70 catalytic activity. Our results provide insights into the fine-tuning of the T cell signaling network before as well as after TCR engagement. The data indicate that the kinase activity of ZAP-70 stimulates negative feedback pathways that target the Src family kinase Lck and modulate the phosphorylation patterns of the immunoreceptor tyrosine-based activation motifs (ITAMs) of the CD3 and ζ-chains, as well as of downstream signaling molecules, including ZAP-70 itself. We developed a computational model that provides a unified mechanistic explanation for the experimental data on ITAM phosphorylation in wild-type cells, ZAP-70-deficient cells, and cells with inhibited ZAP-70 catalytic activity. This model describes the requirements of the ZAP-70 kinase–dependent negative feedback that influences Lck activation, and makes specific predictions for the order in which tyrosines in the ITAMs of TCR ζ-chains must be phosphorylated to be consistent with the experimental data.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:23:42.206.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Arthur Salomon
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	6x(13)C; 6x(13)C; phosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2015-04-07 06:10:29	ID requested
1	2016-05-31 05:44:57	announced
⏵ 2	2024-10-22 04:23:50	announced	2024-10-22: Updated project metadata.

10.1126/scisignal.2005596;

Goodfellow HS, Frushicheva MP, Ji Q, Cheng DA, Kadlecek TA, Cantor AJ, Kuriyan J, Chakraborty AK, Salomon A, Weiss A, The catalytic activity of the kinase ZAP-70 mediates basal signaling and negative feedback of the T cell receptor pathway. Sci Signal, 8(377):ra49(2015) [pubmed]

curator keyword: Biological

submitter keyword: T cell, phosphoproteomics, LC-MS/MS

Arthur Salomon
contact affiliation	Molecular Biology, Cell Biology and Biochemistry Department, Brown University, Providence, RI, USA
contact email	art@drsalomon.com
lab head
Arthur Salomon
contact affiliation	Brown University
contact email	art@drsalomon.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD002023
     1. Label: PRIDE project
     2. Name: The catalytic activity of the kinase Zap-70 mediates basal signaling and negative feedback of the T cell receptor pathway