Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01350 (gastrin)
 9,683 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The homogenate of MC3T3-E1 cells hydrolysed phosphotyrosine, but not phosphoserine or phosphothreonine at acidic pH. It dephosphorylated lysozyme and Raytide (a gastrin analogue peptide) phosphorylated by tyrosine kinase, but showed little activity toward histones phosphorylated by cyclic AMP-dependent protein kinase. Dephosphorylation of phosphorylated lysozyme and Raytide were inhibited by zinc and vanadate, but were insensitive to okadaic acid. These data suggest that the osteoblastic cell line MC3T3-E1 has a phosphotyrosyl protein phosphatase-like activity that may participate in cellular regulation involving protein tyrosine phosphorylation.
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PMID:Phosphotyrosyl protein phosphatase-like activity of a clonal osteoblastic cell line (MC3T3-E1 cell). 865 86

The ptp gene of Acinetobacter johnsonii was previously reported to encode a low-molecular-mass protein, Ptp, whose amino acid sequence, predicted from the theoretical analysis of the nucleotide sequence of the gene, exhibits a high degree of similarity with those of different eukaryotic and prokaryotic phosphotyrosine-protein phophatases. We have now overexpressed the ptp gene in Escherichia coli cells, purified the Ptp protein to homogeneity by a single-step chromatographic procedure, and analysed its functional properties. We have shown that Ptp can catalyse the dephosphorylation of p-nitrophenyl phosphate and phosphotyrosine, but has no effect on phosphoserine or phosphothreonine. Its activity is blocked by ammonium molybdate and sodium orthovanadate, which are strong inhibitors of phosphotyrosine-protein phosphatases, as well as by N-ethylmaleimide and iodoacetic acid. Such specificity of Ptp for phosphotyrosine has been confirmed by the observation that it can dephosphorylate endogenous proteins phosphorylated on tyrosine, but not proteins modified on either serine or threonine. In addition, Ptp has been shown to quantitatively dephosphorylate two exogenous peptides, derived respectively from leech hirudin and human gastrin, previously phosphorylated on tyrosine. Moreover, site-directed mutagenesis experiments performed on Cys11 and Arg16, which are both present in the sequence motif (H/V)C(X5)R(S/T) typical of eukaryotic phosphotyrosine-protein phosphatases, have demonstrated that each amino acid residue is essential for the catalytic activity of Ptp. Taken together, these data provide evidence that Ptp is a member of the phosphotyrosine-protein phosphatase family. Furthermore, in search for the biological function of Ptp, we have found that it can specifically dephosphorylate an endogenous protein kinase, termed Ptk, which is known to autophosphorylate at multiple tyrosine residues in the inner membrane of Acinetobacter johnsonii cells. This represents the first identification of a protein substrate for a bacterial phosphotyrosine-protein phosphatase, and therefore constitutes a possible model for analysing the role of reversible phosphorylation on tyrosine in the regulation of microbial physiology.
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PMID:Functional characterization of the low-molecular-mass phosphotyrosine-protein phosphatase of Acinetobacter johnsonii. 957 Oct 56

The cellular localization of the 35 kDa, low molecular mass acid metallophosphatase (LMW AcPase) from the frog (Rana esculenta) liver and its activity towards P-Ser and P-Tyr phosphorylated peptides were studied. This enzyme was localized to the cytoplasm of hepatocytes but did not appear in other cells of liver tissue (endothelium, macrophages, blood cells). This LMW AcPase does not display activity towards (32)P-phosphorylase a under conditions standard for the enzymes of PPP family. Proteins containing P-Ser: rabbit (32)P-phosphorylasea and phosvitin are hydrolysed only at acidic pH and are poor substrates for this enzyme. The frog AcPase is not inhibited by okadaic acid and F(-) ions, the Ser/Thr protein phosphatase inhibitors. Moreover, the frog enzyme does not cross-react with specific antisera directed against N-terminal fragment of human PP2A and C-terminal conserved fragment of the eukaryotic PP2A catalytic subunits. These results exclude LMW AcPase from belonging to Ser/Thr protein phosphatases: PP1c or PP2Ac. In addition to P-Tyr, this enzyme hydrolyses efficiently at acidic pH P-Tyr phosphorylated peptides (hirudin and gastrin fragments). K(m) value for the hirudin fragment (7.55 +/- 1.59 x 10(-6) M) is 2-3 orders of magnitude lower in comparison with other substrates tested. The enzyme is inhibited competitively by typical inhibitors of protein tyrosine phosphatases (PTPases): sodium orthovanadate, molybdate and tungstate. These results may suggest that the LMW AcPase of frog liver can act as PTPase in vivo. A different cellular localization and different response to inhibition by tetrahedral oxyanions (molybdate, vanadate and tungstate) provide further evidence that LMW AcPase of frog liver is distinct from the mammalian tartrate-resistant acid phosphatases.
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PMID:The 35 kDa acid metallophosphatase of the frog Rana esculenta liver: studies on its cellular localization and protein phosphatase activity. 1283 81

Summary K-ras mutations are found in 40-50% of human colorectal adenomas and carcinomas, but their functional contribution remains incompletely understood. Here, we show that a conditional mutant K-ras mouse model (K-ras(Asp12)/Cre), with transient intestinal Cre activation by beta-Naphthoflavone (beta-NF) treatment, displayed transgene recombination and K-ras(Asp12) expression in the murine intestines, but developed few intestinal adenomas over 2 years. However, when crossed with Apc(Min/+) mice, the K-ras(Asp12)/Cre/Apc(Min/+) offspring showed acceleration of intestinal tumourigenesis with significantly changed average lifespan (P < 0.05) decreased to 18.4 +/- 5.4 weeks from 20.9 +/- 4.7 weeks (control Apc(Min/+) mice). The numbers of adenomas in the small intestine and large intestine were significantly (P < 0.01) increased by 1.5-fold and 5.7-fold, respectively, in K-ras(Asp12)/Cre/Apc(Min/+) mice compared with Apc(Min/+) mice, with the more marked increase in adenoma prevalence in the large intestine. To explore possible mechanisms for K-ras(Asp12) and Apc(Min) co-operation, the Mitogen-activated protein kinase (Mapk), Akt and Wnt signalling pathways, including selected target gene expression levels, were evaluated in normal large intestine and large intestinal tumours. K-ras(Asp12) increased activation of Mapk and Akt signalling pathway targets phospho-extracellular signal-regulated kinase (pErk) and pAkt, and increased relative expression levels of Wnt pathway targets vascular endothelial growth factor (VEGF), gastrin, cyclo-oxygenase 2 (Cox2) and T-cell lymphoma invasion and metastasis 1 (Tiam1) in K-ras(Asp12)/Cre/Apc(Min/+) adenomas compared with that of Apc(Min/+) adenomas, although other Wnt signalling pathway target genes such as Peroxisome proliferator-activated receptor delta (PPARd), matrix metalloproteinase 7 (MMP7), protein phosphatase 1 alpha (PP1A) and c-myc remained unchanged. In conclusion, intestinal expression of K-ras(Asp12) promotes mutant Apc-initiated intestinal adenoma formation in vivo more in the large intestine than the small intestine, with evidence of synergistic co-operation between mutant K-ras and Apc involving increased expression of some Wnt-pathway target genes.
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PMID:Mutated K-ras(Asp12) promotes tumourigenesis in Apc(Min) mice more in the large than the small intestines, with synergistic effects between K-ras and Wnt pathways. 1976 10