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Title of the item:

Serine Phosphorylation of SLP76 Is Dispensable for T Cell Development but Modulates Helper T Cell Function.

Title :
Serine Phosphorylation of SLP76 Is Dispensable for T Cell Development but Modulates Helper T Cell Function.
Authors :
Navas, Victor H.
Cuche, Céline
Alcover, Andres
Di Bartolo, Vincenzo
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Subject Terms :
ADAPTOR proteins
T helper cells
Source :
PLoS ONE; 1/20/2017, Vol. 12 Issue 1, p1-17, 17p
Academic Journal
The adapter protein SLP76 is a key orchestrator of T cell receptor (TCR) signal transduction. We previously identified a negative feedback loop that modulates T cell activation, involving phosphorylation of Ser376 of SLP76 by the hematopoietic progenitor kinase 1 (HPK1). However, the physiological relevance of this regulatory mechanism was still unknown. To address this question, we generated a SLP76-S376A-expressing knock-in mouse strain and investigated the effects of Ser376 mutation on T cell development and function. We report here that SLP76-S376A-expressing mice exhibit normal thymocyte development and no detectable phenotypic alterations in mature T cell subsets or other lymphoid and myeloid cell lineages. Biochemical analyses revealed that mutant T cells were hypersensitive to TCR stimulation. Indeed, phosphorylation of several signaling proteins, including SLP76 itself, phospholipase Cγ1 and the protein kinases AKT and ERK1/2, was increased. These modifications correlated with increased Th1-type and decreased Th2-type cytokine production by SLP76-S376A T cells, but did not result in significant changes of proliferative capacity nor activation-induced cell death susceptibility. Hence, our results reveal that SLP76-Ser376 phosphorylation does not mediate all HPK1-dependent regulatory effects in T cells but it fine-tunes helper T cell responses. [ABSTRACT FROM AUTHOR]
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