SHP-1 (PTP1C, SH-PTP1, SHP, HCP) and SHP-2 (PTP2C, SH-PTP-2, PTP1D, Syp, SH-PTP-3) are two SH2 domain containing protein tyrosine phosphatases (PTPs) which have crucial roles in signal transduction. The goal of this study is to investigate the role of these enzymes in the signaling of platelet derived growth factor (PDGF). The experimental approach is to co-express transiently the PDGF receptor with native, truncated, mutated, chimeric, and hybrid forms of the enzymes in a well established 293 cell expression system. Such gene manipulations are intended to change the activity, substrate specificity, regulation, ability to interact with other proteins, and localization of SHP-1 and SHP-2. The objectives are to determine the effects of such altered PTP expressions on tyrosine phosphorylation of the PDGF receptor and on activation of the Ras/MAP kinase and JAK-STAT signaling pathways. By correlating activity of the PTPs, tyrosine phosphorylation of the PDGF receptor and activation of MAP kinase STATs, the intent is to obtain a better understanding of the regulatory mechanism of SHP-1 and SHP-2, better define the distinct functions of the enzymes, delineate the roles of individual phosphorylation sites of PDGF-R and proteins recruited to the sites, and produce more complete diagrams for the two major signal transduction pathways.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
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Physiological Chemistry Study Section (PC)
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Vanderbilt University Medical Center
Internal Medicine/Medicine
Schools of Medicine
United States
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Zhao, Runxiang; Fu, Xueqi; Teng, Lirong et al. (2003) Blocking the function of tyrosine phosphatase SHP-2 by targeting its Src homology 2 domains. J Biol Chem 278:42893-8
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Zhao, Runxiang; Zhao, Zhizhuang Joe (2003) Identification of a variant form of PZR lacking immunoreceptor tyrosine-based inhibitory motifs. Biochem Biophys Res Commun 303:1028-33
Xiong, Huaqi; Chen, Yongxiong; Yi, Yajun et al. (2002) A novel gene encoding a TIG multiple domain protein is a positional candidate for autosomal recessive polycystic kidney disease. Genomics 80:96-104
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Zhao, Runxiang; Guerrah, Abdelmadjid; Tang, Hua et al. (2002) Cell surface glycoprotein PZR is a major mediator of concanavalin A-induced cell signaling. J Biol Chem 277:7882-8
Xu, Ming-jiang; Zhao, Runxiang; Cao, Hongxi et al. (2002) SPAP2, an Ig family receptor containing both ITIMs and ITAMs. Biochem Biophys Res Commun 293:1037-46
Qi, Ying; Zhao, Runxiang; Cao, Hongxi et al. (2002) Purification and characterization of protein tyrosine phosphatase PTP-MEG2. J Cell Biochem 86:79-89
Yang, J; Niu, T; Zhang, A et al. (2001) Relation between the flexibility of the WPD loop and the activity of the catalytic domain of protein tyrosine phosphatase SHP-1. J Cell Biochem 84:47-55
Zhao, R; Qi, Y; Chen, J et al. (2001) FYVE-DSP2, a FYVE domain-containing dual specificity protein phosphatase that dephosphorylates phosphotidylinositol 3-phosphate. Exp Cell Res 265:329-38

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