Low molecular weight protein tyrosine phosphatases: small, but smart.
ABSTRACT Low molecular weight protein tyrosine phosphatases (LMW-PTPs) are a family of 18-kDa enzymes involved in cell growth regulation. Despite very limited sequence similarity to the PTP superfamily, they display a conserved signature motif in the catalytic site. LMW-PTP associates and dephosphorylate many growth factor receptors, such as platelet-derived growth factor receptor (PDGF-r), insulin receptor and ephrin receptor, thus downregulating many of the tyrosine kinase receptor functions that lead to cell division. In particular, LMW-PTP acts on both growth-factor-induced mitosis, through dephosphorylation of activated PDGF-r, and on cytoskeleton rearrangement, through dephosphorylation of p190RhoGAP and the consequent regulation of the small GTPase Rho. LMW-PTP activity is modulated by tyrosine phosphorylation on two specific residues, each of them with specific characteristics. LMW-PTP activity on specific substrates depends also on its localization. Moreover, LMW-PTP is reversibly oxidized during growth factor signaling, leading to inhibition of its enzymatic activity. Recovery of phosphatase activity depends on the availability of reduced glutathione and involves the formation of an S-S bridge between the two catalytic site cysteines. Furthermore, studies on the redox state of LMW-PTP in contact-inhibited cells and in mature myoblasts suggest that LMW-PTP is a general and versatile modulator of growth inhibition.
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ABSTRACT: Entamoeba histolytica is a eukaryotic intestinal parasite of humans, and is endemic in developing countries. We have characterized the E. histolytica putative low molecular weight protein tyrosine phosphatase (LMW-PTP). The structure for this amebic tyrosine phosphatase was solved, showing the ligand-induced conformational changes necessary for binding of substrate. In amebae, it was expressed at low but detectable levels as detected by immunoprecipitation followed by immunoblotting. A mutant LMW-PTP protein in which the catalytic cysteine in the active site was replaced with a serine lacked phosphatase activity, and was used to identify a number of trapped putative substrate proteins via mass spectrometry analysis. Seven of these putative substrate protein genes were cloned with an epitope tag and overexpressed in amebae. Five of these seven putative substrate proteins were demonstrated to interact specifically with the mutant LMW-PTP. This is the first biochemical study of a small tyrosine phosphatase in Entamoeba, and sets the stage for understanding its role in amebic biology and pathogenesis.Molecular and Biochemical Parasitology 02/2014; 193(1):33-44. · 2.73 Impact Factor
- Bulletin- Korean Chemical Society 01/2009; 30(1). · 0.84 Impact Factor
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ABSTRACT: Recent studies showed that the serum alkaline phosphatase is an independent predictor of the coronary artery disease (CAD). In this work, we aimed to summarize the association between three phosphatase related single nucleotide polymorphisms (rs12526453, rs11066301 and rs3828329) and the risk of CAD in Han Chinese. Our results showed that the rs3828329 of the ACP1 gene was closely related to the risk of CAD in Han Chinese (OR = 1.45, p = 0.0006). This significant association of rs3828329 with CAD was only found in the females (Additive model: OR = 1.80, p = 0.001; dominant model: OR = 1.69, p = 0.03; recessive model: OR = 1.96, p = 0.0008). Moreover, rs3828329 was likely to exert its effect in females aged 65 years and older (OR = 2.27, p = 0.001). Further meta-analyses showed that the rs12526453 of PHACTR11 gene (OR = 1.14, p < 0.0001, random-effect method) and the rs11066301 of PTPN11 gene (OR = 1.15, p < 0.0001, fixed-effects method) were associated with CAD risk in multiple populations. Our results showed that the polymorphisms rs12526453 and rs11066301 are significantly associated with the CAD risk in multiple populations. The rs3828329 of ACP1 gene is also a risk factor of CAD in Han Chinese females aged 65 years and older.International Journal of Molecular Sciences 01/2014; 15(8):14058-76. · 2.46 Impact Factor