错义突变
癌症研究
癌基因
生物
酪氨酸激酶
突变
乳头状肾细胞癌
激酶
点突变
肾
基因
遗传学
受体
细胞周期
作者
Laura S. Schmidt,Kerstin Junker,Noboru Nakaigawa,Tracy Kinjerski,Gregor Weirich,Maria Miller,Irina A. Lubensky,Hartmut P.H. Neumann,Hiltrud Brauch,Johann Decker,Cathy D. Vocke,James A. Brown,Robert B. Jenkins,Rosette Lidereau,Ulf S.R. Bergerheim,Bernard Gerrard,Michael Dean,W. Marston Linehan,Berton Zbar
出处
期刊:Oncogene
[Springer Nature]
日期:1999-04-08
卷期号:18 (14): 2343-2350
被引量:493
标识
DOI:10.1038/sj.onc.1202547
摘要
Hereditary papillary renal carcinoma (HPRC) is characterized by multiple, bilateral papillary renal carcinomas. Previously, we demonstrated missense mutations in the tyrosine kinase domain of the MET proto-oncogene in HPRC and a subset of sporadic papillary renal carcinomas. In this study, we screened a large panel of sporadic papillary renal carcinomas and various solid tumors for mutations in the MET proto-oncogene. Summarizing these and previous results, mutations of the MET proto-oncogene were detected in 17/129 sporadic papillary renal carcinomas but not in other solid tumors. We detected five novel missense mutations; three of five mutations were located in the ATP-binding region of the tyrosine kinase domain of MET. One novel mutation in MET, V1110I, was located at a codon homologous to an activating mutation in the c-erbB proto-oncogene. These mutations caused constitutive phosphorylation of MET when transfected into NIH3T3 cells. Molecular modeling studies suggest that these activating mutations interfere with the intrasteric mechanism of tyrosine kinase autoinhibition and facilitate transition to the active form of the MET kinase. The low frequency of MET mutations in noninherited papillary renal carcinomas (PRC) suggests that noninherited PRC may develop by a different mechanism than hereditary papillary renal carcinoma.
科研通智能强力驱动
Strongly Powered by AbleSci AI