PXD008258

PXD008258 is an original dataset announced via ProteomeXchange.

Title	Lck promotes Zap70-dependent LAT phosphorylation by bridging Zap70 to LAT
Description	T cell antigen receptor (TCR) signaling depends upon the kinases Lck and Zap70. Lck phosphorylates the TCR, facilitating Zap70 recruitment to the stimulated TCR. Lck also phosphorylates Zap70, relieving its auto-inhibition and activating its catalytic domain. Zap70 then phosphorylates the critical adaptors LAT and SLP76 which serve to nucleate key effector molecules required for downstream responses. However, mechanisms facilitating the interaction of Zap70 with its substrates have not been described. We report an evolutionarily conserved proline-rich motif in LAT is important for Zap70-induced phosphorylation of LAT and downstream signaling. This LAT proline-rich motif associated with the Lck SH3 domain, thereby facilitating Zap70-mediated phosphorylation of LAT and downstream functions. Our results suggest Lck orchestrates multiple steps in TCR signaling including the newly described facilitation of the interaction of Zap70 with its substrate LAT. This previously unrecognized feature of TCR proximal signaling may contribute to the development of more immunomodulatory therapies.
HostingRepository	PRIDE
AnnounceDate	2019-11-12
AnnouncementXML	Submission_2019-11-12_10:10:25.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	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2017-11-21 08:36:37	ID requested
⏵ 1	2019-11-12 10:10:27	announced

Lo WL, Shah NH, Ahsan N, Horkova V, Stepanek O, Salomon AR, Kuriyan J, Weiss A, Lck promotes Zap70-dependent LAT phosphorylation by bridging Zap70 to LAT. Nat Immunol, 19(7):733-741(2018) [pubmed]

ProteomeXchange project tag: Biology/Disease-Driven Human Proteome Project (B/D-HPP), Human Proteome Project

submitter keyword: Jurkat T cell line, Mice, Lck, Zap70, LAT, TCR signaling

Arthur R. Salomon
contact affiliation	Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, RI 02912, USA
contact email	art@drsalomon.com
lab head
Arthur Salomon
contact affiliation	Brown University
contact email	art@drsalomon.com
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2019/11/PXD008258

PRIDE project URI

• PRIDE
  1. PXD008258
     1. Label: PRIDE project
     2. Name: Lck promotes Zap70-dependent LAT phosphorylation by bridging Zap70 to LAT