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A novel pathway down-modulating T cell activation involves HPK-1-dependent recruitment of 14-3-3 proteins on SLP-76.

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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https://hal-pasteur.archives-ouvertes.fr/pasteur-01372621
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Submitted on : Tuesday, September 27, 2016 - 2:37:55 PM
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Vincenzo Di Bartolo, Benjamin Montagne, Mogjiborahman Salek, Britta Jungwirth, Florent Carrette, et al.. A novel pathway down-modulating T cell activation involves HPK-1-dependent recruitment of 14-3-3 proteins on SLP-76.. Journal of Experimental Medicine, Rockefeller University Press, 2007, 204 (3), pp.681-91. ⟨10.1084/jem.20062066⟩. ⟨pasteur-01372621⟩

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