A Novel Pathway Down-modulating T Cell Activation Involves HPK-1-dependent Recruitment of 14-3-3 Proteins on SLP-76

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 2007 Mar 14

PMID 17353368

Citations 50

Authors

Vincenzo Di Bartolo

Benjamin Montagne

Mogjiborahman Salek

Britta Jungwirth

Florent Carrette

Julien Fourtane

Nathalie Sol-Foulon

Frederique Michel

Olivier Schwartz

Wolf D Lehmann

Oreste Acuto

Affiliations

Soon will be listed here.

Abstract

The SH2 domain-containing leukocyte protein of 76 kD (SLP-76) is a pivotal element of the signaling machinery controlling T cell receptor (TCR)-mediated activation. Here, we identify 14-3-3epsilon and zeta proteins as SLP-76 binding partners. This interaction was induced by TCR ligation and required phosphorylation of SLP-76 at serine 376. Ribonucleic acid interference and in vitro phosphorylation experiments showed that serine 376 is the target of the hematopoietic progenitor kinase 1 (HPK-1). Interestingly, either S376A mutation or HPK-1 knockdown resulted in increased TCR-induced tyrosine phosphorylation of SLP-76 and phospholipase C-gamma1. Moreover, an SLP-76-S376A mutant induced higher interleukin 2 gene transcription than wild-type SLP-76. These data reveal a novel negative feedback loop involving HPK-1-dependent serine phosphorylation of SLP-76 and 14-3-3 protein recruitment, which tunes T cell activation.

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