Phosphotyrosine Phosphatase (phosphotyrosine + phosphatase)

Distribution by Scientific Domains


Selected Abstracts


Quinolinic acid modulates the activity of src family kinases in rat striatum: in vivo and in vitro studies

JOURNAL OF NEUROCHEMISTRY, Issue 5 2006
Alessio Metere
Abstract Quinolinic acid (QA) has been shown to evoke neurotoxic events via NMDA receptor (NMDAR) overactivation and oxidative stress. NMDARs are particularly vulnerable to free radicals, which can modulate protein tyrosine kinase (PTK) and phosphotyrosine phosphatase (PTP) activities. The src family of tyrosine kinases are associated with the NMDAR complex and regulate NMDA channel function. Because QA is an NMDAR agonist as well as a pro-oxidant agent, we investigated whether it may affect the activity of PTKs and PTPs in vivo and in vitro. In synaptosomes prepared from striata dissected 15 min, 30 min or 15 days after bilateral injection of QA we observed modulation of the phosphotyrosine pattern; a significant decrease in PTP activity; and a sustained increase in c-src and lyn activity at 15 and 30 min after treatment with QA, followed by a decrease 2 weeks later. Striatal synaptosomes treated in vitro with QA showed time- and dose-dependent modulation of c-src and lyn kinase activities. Moreover, the nitric oxide synthase inhibitor NG -nitro- l -arginine-methyl ester, the NMDAR antagonist d -2-amino-5-phosphonovaleric acid and pyruvate suppressed the QA-induced modulation of c-src activity. These findings suggest a novel feature of QA in regulating src kinase activity through the formation of reactive radical species and/or NMDAR overactivation. [source]


Simultaneous Detection of ACP1 and GC Genotypes Using PCR/SSCP

ANNALS OF HUMAN GENETICS, Issue 1 2003
J. Dissing
Summary The classical enzyme and protein markers ACP1 and GC have gained new importance because of the biological functions of their gene products. ACP1 encodes a low molecular weight enzyme which is now recognized as a phosphotyrosine phosphatase with a role in the regulation of signal transduction pathways, and GC-globulin acts both as a transporter of vitamin D and as a plasma actin scavenger and plays a role in macrophage activation. These two polymorphisms were phenotyped for decades on the basis of electrophoretic isozyme or protein patterns; the gene structures are now known. Nucleotide substitutions determining the common alleles are close enough at each locus to be contained in one short PCR product. We have developed a simple, rapid and reliable multiplex method based on PCR and SSCP which allows the simultaneous determination of the common ACP1 and GC genotypes. [source]


Somatostatin receptor activation (sst1,sst5) differentially influences human retinal pigment epithelium cell viability

ACTA OPHTHALMOLOGICA, Issue 6 2010
Thekla Papadaki
Abstract. Purpose:, To investigate the differential effects of somatostatin and its receptors (sst1,5) on the viability of cultured human retinal pigment epithelium (hRPE) cells. Methods:, MTT [3 (4, 5-dimethylthiazol-2yl)-2, 5 diphenyltetrazolium bromide], APO PercentageTM and trypan blue assays were performed to assess the mechanisms via which somatostatin (10,10,10,4 m) and selective receptor (sst1,5) ligands (10,12,10,4 m) affect cell viability. The effect of orthovanadate (phosphatase inhibitor, 10,7,10,5 m) on somatostatin's (10,5 m) actions was examined, and western blot analysis was employed to determine the presence of ssts and phosphotyrosine phosphatase SHP-1 in human RPE cells. Results:, Somatostatin and selective ligands for the five somatostatin receptor subtypes (sst1,5) decreased cell viability in a concentration-dependent manner. The observed decrease in cell number was partly because of apoptosis via the activation of sst1 and sst5 receptors. Activation of sst2, sst3 and sst4 receptors led to inhibition of cell growth that did not involve apoptosis, but rather antiproliferative actions. SHP-1 was found in the human RPE cells and sodium orthovanadate reversed somatostatin's actions. Conclusions:, This study provides new information regarding the involvement of ssts in human RPE cell viability and suggests that a pathway involving the phosphotyrosine phosphatase may mediate somatostatin's actions. [source]


L -NAME reverses quinolinic acid-induced toxicity in rat corticostriatal slices: Involvement of src family kinases

JOURNAL OF NEUROSCIENCE RESEARCH, Issue 12 2007
Cinzia Mallozzi
Abstract Quinolinic acid (QA) is an endogenous excitotoxin acting on N -methyl- d -aspartate receptors (NMDARs) that leads to the pathologic and neurochemical features similar to those observed in Huntington's disease (HD). The mechanism of QA toxicity also involves free radicals formation and oxidative stress. NMDARs are particularly vulnerable to the action of reactive oxygen species (ROS) and reactive nitrogen species (RNS) that can act as modulators of the activity of protein tyrosine kinases (PTKs) and phosphotyrosine phosphatases (PTPs). Because QA is able to activate neuronal nitric oxide synthase (nNOS) as well as to stimulate the NMDARs, we evaluated the effect of N,-Nitro- l -arginine-methyl ester (l -NAME), a selective nNOS inhibitor, on QA-induced neurotoxicity in rat corticostriatal slices. In electrophysiologic experiments we observed that slice perfusion with QA induced a strong reduction of field potential (FP) amplitude, followed by a partial recovery at the end of the QA washout. In the presence of l -NAME the recovery of FP amplitude was significantly increased with respect to QA alone. In synaptosomes, prepared from corticostriatal slices after the electrophysiologic recordings, we observed that l -NAME pre-incubation reversed the QA-mediated inhibitory effects on protein tyrosine phosphorylation pattern, c-src, lyn, and fyn kinase activities and tyrosine phosphorylation of NMDAR subunit NR2B, whereas the PTP activity was not recovered in the presence of l -NAME. These findings suggest that NO plays a key role in the molecular mechanisms of QA-mediated excitotoxicity in experimental model of HD. 2007 Wiley-Liss, Inc. [source]