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Miller G 《Science (New York, N.Y.)》2004,304(5667):34-36
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Wang Z Shen D Parsons DW Bardelli A Sager J Szabo S Ptak J Silliman N Peters BA van der Heijden MS Parmigiani G Yan H Wang TL Riggins G Powell SM Willson JK Markowitz S Kinzler KW Vogelstein B Velculescu VE 《Science (New York, N.Y.)》2004,304(5674):1164-1166
Tyrosine phosphorylation, regulated by protein tyrosine phosphatases (PTPs) and kinases (PTKs), is important in signaling pathways underlying tumorigenesis. A mutational analysis of the tyrosine phosphatase gene superfamily in human cancers identified 83 somatic mutations in six PTPs (PTPRF, PTPRG, PTPRT, PTPN3, PTPN13, PTPN14), affecting 26% of colorectal cancers and a smaller fraction of lung, breast, and gastric cancers. Fifteen mutations were nonsense, frameshift, or splice-site alterations predicted to result in truncated proteins lacking phosphatase activity. Five missense mutations in the most commonly altered PTP (PTPRT) were biochemically examined and found to reduce phosphatase activity. Expression of wild-type but not a mutant PTPRT in human cancer cells inhibited cell growth. These observations suggest that the mutated tyrosine phosphatases are tumor suppressor genes, regulating cellular pathways that may be amenable to therapeutic intervention. 相似文献
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Identification of the cystic fibrosis gene: chromosome walking and jumping 总被引:253,自引:0,他引:253
J M Rommens M C Iannuzzi B Kerem M L Drumm G Melmer M Dean R Rozmahel J L Cole D Kennedy N Hidaka 《Science (New York, N.Y.)》1989,245(4922):1059-1065
An understanding of the basic defect in the inherited disorder cystic fibrosis requires cloning of the cystic fibrosis gene and definition of its protein product. In the absence of direct functional information, chromosomal map position is a guide for locating the gene. Chromosome walking and jumping and complementary DNA hybridization were used to isolate DNA sequences, encompassing more than 500,000 base pairs, from the cystic fibrosis region on the long arm of human chromosome 7. Several transcribed sequences and conserved segments were identified in this cloned region. One of these corresponds to the cystic fibrosis gene and spans approximately 250,000 base pairs of genomic DNA. 相似文献
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Increased insulin sensitivity and obesity resistance in mice lacking the protein tyrosine phosphatase-1B gene 总被引:1,自引:0,他引:1
Elchebly M Payette P Michaliszyn E Cromlish W Collins S Loy AL Normandin D Cheng A Himms-Hagen J Chan CC Ramachandran C Gresser MJ Tremblay ML Kennedy BP 《Science (New York, N.Y.)》1999,283(5407):1544-1548
Protein tyrosine phosphatase-1B (PTP-1B) has been implicated in the negative regulation of insulin signaling. Disruption of the mouse homolog of the gene encoding PTP-1B yielded healthy mice that, in the fed state, had blood glucose concentrations that were slightly lower and concentrations of circulating insulin that were one-half those of their PTP-1B+/+ littermates. The enhanced insulin sensitivity of the PTP-1B-/- mice was also evident in glucose and insulin tolerance tests. The PTP-1B-/- mice showed increased phosphorylation of the insulin receptor in liver and muscle tissue after insulin injection in comparison to PTP-1B+/+ mice. On a high-fat diet, the PTP-1B-/- and PTP-1B+/- mice were resistant to weight gain and remained insulin sensitive, whereas the PTP-1B+/+ mice rapidly gained weight and became insulin resistant. These results demonstrate that PTP-1B has a major role in modulating both insulin sensitivity and fuel metabolism, thereby establishing it as a potential therapeutic target in the treatment of type 2 diabetes and obesity. 相似文献
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