Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

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.

Original publication

DOI

10.1084/jem.20062066

Type

Journal article

Journal

J Exp Med

Publication Date

19/03/2007

Volume

204

Pages

681 - 691

Keywords

14-3-3 Proteins, Adaptor Proteins, Signal Transducing, Animals, COS Cells, Cercopithecus aethiops, Down-Regulation, Humans, Jurkat Cells, Lymphocyte Activation, Phosphoproteins, Phosphorylation, Protein Binding, Protein-Serine-Threonine Kinases, Serine, Signal Transduction, T-Lymphocytes