Tyrosine kinase receptor indistinguishable from the c-met protein
S Giordano, C Ponzetto, MFD Renzo, CS Cooper… - Nature, 1989 - nature.com
Nature, 1989•nature.com
GROWTH factor receptors with protein tyrosine kinase activity are central to the control of
proliferation of both normal and malignant cells1–3. 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) …
proliferation of both normal and malignant cells1–3. 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) …
Abstract
GROWTH factor receptors with protein tyrosine kinase activity are central to the control of proliferation of both normal and malignant cells1–3. 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.
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