Linked Life Data

8183564

Source:http://linkedlifedata.com/resource/pubmed/id/8183564

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
1994-6-14
pubmed:abstractText
The MET gene, encoding the tyrosine kinase receptor for Hepatocyte Growth Factor, is a potentially harmful oncogene overexpressed in a significant fraction of human cancers. To study the molecular mechanisms responsible for oncogenic activation, the biochemical and biological properties of a number of MET constructs were analysed. The native heterodimeric receptor (alpha beta), the beta chain alone, as well as a kinase defective mutant did not transform rodent fibroblasts upon transfection. The cytoplasmic domain, truncated immediately below the transmembrane region, acquired constitutive tyrosine kinase activity in vivo, produced foci of transformation, and was tumorigenic in nude mice. Removal of the first 39 amino acids of the juxtamembrane domain resulted in loss of constitutive activation in vivo and transforming potential, without impairment of the in vitro kinase activity. Replacement of the juxtamembrane domain with 5' TPR sequences restored constitutive kinase activation and transforming properties. Site-directed mutagenesis of either of the two tyrosine residues involved in the positive regulation of the catalytic activity upon phosphorylation (Y1234 or Y1235 in the kinase domain of the HGF receptor), strongly impaired TRP-MET transforming potential. These data show that: (1) the truncated cytoplasmic HGF receptor has constitutive kinase activity and is oncogenic; (2) the first 39 amino acids of the juxtamembrane domain and (3) the regulatory tyrosines in the catalytic domain are required to unleash its transforming potential.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0950-9232
pubmed:author
pubmed:issnType
Print
pubmed:volume
9
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1691-7
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
1994
pubmed:articleTitle
Structural and functional domains critical for constitutive activation of the HGF-receptor (Met).
pubmed:affiliation
Department of Biomedical Sciences and Oncology, University of Torino Medical School, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't