TAILIEUCHUNG - Báo cáo khoa học: SHP-1 dephosphorylates 3BP2 and potentially downregulates 3BP2-mediated T cell antigen receptor signaling

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. | ềFEBS Journal SHP-1 dephosphorylates 3BP2 and potentially downregulates 3BP2-mediated T cell antigen receptor signaling Zhenbao Yu1 Meryem Maoui1 Zhizhuang J. Zhao2 Yang Li1 and Shi-Hsiang Shen1 3 1 Health Sector Biotechnology Research Institute NationalResearch Councilof Canada Montreal Canada 2 Department of Pathology University of Oklahoma Health Sciences Center Oklahoma City OK USA 3 Department of Medicine McGillUniversity Montreal Canada Keywords 3BP2 protein phosphatases protein-protein interaction SHP-1 T cell-receptor Correspondence Zhenbao Yu Health Sector Biotechnology Research Institute NationalResearch Councilof Canada Montreal Quebec H4P 2R2 Canada Fax 1 514 496 6319 Tel 1 514 496 6377 E-mail Received 14 December 2005 revised 28 February 2006 accepted 16 March 2006 doi 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. Protein tyrosine phosphorylation plays a critical role in various signal-transduction pathways in T lymphocytes

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