Tyrosine kinase receptor indistinguishable from the c-met protein

Abstract

GROWTH factor receptors with protein tyrosine kinase activity are central to the control of proliferation of both normal and malignant cells^1–3. Using anti-phosphotyrosine antibodies⁴, we have previously identified a transmembrane glycoprotein with abnormally high protein tyrosine kinase activity in a human gastric tumour cell line (GTL-16)^5,6. 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 αβ-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 protooncogene and that the αβ-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.