Receptor-like oncogenes: functional analysis through novel experimental approaches.
A growing proportion of the known protooncogenes encode putative receptors for growth/differentiation factors. The detection and identification of the hypothetical ligands of these presumed receptors, and the elucidation of their biological roles constitute a new biochemical challenge. Employing the neu protooncogene, here three experimental approaches to these problems are described. Stimulatory anti-receptor antibodies appear to mimic the action of the presumptive ligand of the neu receptor, and also lead to the conclusion that the oncogenic receptor, unlike the normal p185neu, is functionally equivalent to a ligand-stimulated receptor. Second, an experimental strategy was developed for the detection of the neu ligand. Employing this approach a candidate ligand was detected in the growth medium of certain oncogene-transformed fibroblasts. Thirdly, engineered chimeras of the neu gene and the gene for the EGF-receptor enabled construction of a neu receptor that is responsive to a heterologous ligand. Combinely, these approaches may provide a detailed biological picture of the action of the putative ligand, and may be generally applicable in the study of other receptor-like oncogenic proteins.
Yarden
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Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel.
D000818:Animals; D006801:Humans; D009857:Oncogenes / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D018719:Erb-b2 Receptor Tyrosine Kinases; D011956:Receptors, Cell Surface
D011518:Proto-Oncogene Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D011956:Receptors, Cell Surface