Tyrosine kinase receptor indistinguishable from the c-met protein.
Growth factor receptors with protein tyrosine kinase activity are central to the control of proliferation of both normal and malignant cells. Using anti-phosphotyrosine antibodies, we have previously identified a transmembrane glycoprotein with abnormally high protein tyrosine kinase activity in a human gastric tumour cell line (GTL-16). Electrophoresis under non-reducing conditions revealed that this kinase (relative molecular mass 145,000 (145 K)) is disulphide-linked to a 50K chain in an alpha beta-complex of 190K (p190). From its novel two-chain structure, we deduced that p190 was the prototype of a new class of tyrosine kinase receptors. We now show that p190 is indistinguishable from the protein encoded by the c-met proto-oncogene and that the alpha beta-subunit structure is conserved in other human cell lines. We also show that the high level of p190 found in the GTL-16 cell line is accompanied by amplification and overexpression of c-met. This provides the first example of a functional alteration of c-met in a human tumour cell line.
Giordano
S
S
Department of Biomedical Sciences and Oncology, University of Torino, Italy.
Ponzetto
C
C
Di Renzo
M F
MF
Cooper
C S
CS
Comoglio
P M
PM
D002460:Cell Line; D066246:ErbB Receptors; D005784:Gene Amplification; D006801:Humans; D011505:Protein-Tyrosine Kinases / Q000737:chemistry*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000737:chemistry; D019859:Proto-Oncogene Proteins c-met; D013274:Stomach Neoplasms / Q000378:metabolism
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D019859:Proto-Oncogene Proteins c-met