SHP-1 dephosphorylates 3BP2 and potentially downregulates 3BP2-mediated T cell antigen receptor signaling

The FEBS Journal
Zhenbao YuShi-Hsiang Shen

Abstract

Src homology 2 (SH2) domain-containing protein tyrosine phosphatase-1 (SHP-1) is a critical inhibitory regulator in T cell-receptor (TCR) signaling. However, the exact molecular mechanism underlying this is poorly defined, largely because the physiological substrates for SHP-1 in T cells remain elusive. In this study, we showed that adaptor protein 3BP2 serves as a binding protein and a physiological substrate of SHP-1. 3BP2 is phosphorylated on tyrosyl residue 448 in response to TCR activation, and the phosphorylation is required for T cell signalling, as indicated by transcriptional activation of nuclear factor activated in T cells (NFAT). Concurrently, phosphorylation of Tyr566 at the C-terminus of SHP-1 causes specific recruitment of 3BP2 to the phosphatase through the SH2 domain of the adaptor protein. This leads to efficient dephosphorylation of 3BP2 and thereby termination of T cell signaling. The study thus defines a novel function of the C-terminal segment of SHP-1 and reveals a new mechanism by which T cell signaling is regulated.

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Citations

Mar 3, 2011·Immunologic Research·Lindsay J Edwards, Brian D Evavold
Feb 13, 2007·Annual Review of Immunology·Lily I PaoBenjamin G Neel
Jun 1, 2012·Orphanet Journal of Rare Diseases·Ernst J ReichenbergerSteven A Lietman
Jul 1, 2014·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Teruhito YoshitakaYasuyoshi Ueki
Jun 12, 2014·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Tomoyuki MukaiYasuyoshi Ueki
Aug 17, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Erola Ainsua-EnrichMargarita Martín
Sep 25, 2014·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Wei-Tien TaiKuen-Feng Chen

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