{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T20:26:39Z","timestamp":1791404799129,"version":"4.3.3"},"reference-count":55,"publisher":"National Academy of Sciences","issue":"21","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1997,10,14]]},"abstract":"<jats:p>\n                    Recently, mutations in the Met tyrosine kinase receptor have been identified in both hereditary and sporadic forms of papillary renal carcinoma. We have introduced the corresponding mutations into the\n                    <jats:italic>met<\/jats:italic>\n                    cDNA and examined the effect of each mutation in biochemical and biological assays. We find that the Met mutants exhibit increased levels of tyrosine phosphorylation and enhanced kinase activity toward an exogenous substrate when compared with wild-type Met. Moreover, NIH 3T3 cells expressing mutant Met molecules form foci\n                    <jats:italic>in vitro<\/jats:italic>\n                    and are tumorigenic in nude mice. Enzymatic and biological differences were evident among the various mutants examined, and the somatic mutations were generally more active than those of germ-line origin. A strong correlation between the enzymatic and biological activity of the mutants was observed, indicating that tumorigenesis by Met is quantitatively related to its level of activation. These results demonstrate that the Met mutants originally identified in human papillary renal carcinoma are oncogenic and thus are likely to play a determinant role in this disease, and these results raise the possibility that activating Met mutations also may contribute to other human malignancies.\n                  <\/jats:p>","DOI":"10.1073\/pnas.94.21.11445","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:35:50Z","timestamp":1027679750000},"page":"11445-11450","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":373,"title":["Activating mutations for the Met tyrosine kinase receptor in human\u2009cancer"],"prefix":"10.1073","volume":"94","author":[{"given":"Michael","family":"Jeffers","sequence":"first","affiliation":[{"name":"Advanced BioScience Laboratories\u2013Basic Research Program and Laboratory of Immunobiology, National Cancer Institute\u2013Frederick Cancer Research and Development Center, Frederick, MD 21702; Intramural Research Support Program, Scientific Applications International Corporation, Frederick, MD 21702; and Department of Urology, Yokohama City University School of Medicine, 3\u20139 Fukuura, Kanazawa-ku, Yokohama 236 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Advanced BioScience Laboratories\u2013Basic Research Program and Laboratory of Immunobiology, National Cancer Institute\u2013Frederick Cancer Research and Development Center, Frederick, MD 21702; Intramural Research Support Program, Scientific Applications International Corporation, Frederick, MD 21702; and Department of Urology, Yokohama City University School of Medicine, 3\u20139 Fukuura, Kanazawa-ku, Yokohama 236 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noboru","family":"Nakaigawa","sequence":"additional","affiliation":[{"name":"Advanced BioScience 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