THE PROTOONCOGENE C-SEA ENCODES A TRANSMEMBRANE PROTEIN-TYROSINE KINASE RELATED TO THE MET HEPATOCYTE GROWTH-FACTOR SCATTER FACTOR-RECEPTOR

c-sea is the cellular homologue of the avian erythroblastosis virus S13-encoded oncogene v-sea. We have isolated and determined the nucleotide sequence of overlapping chicken cDNAs that encode the putative c-sea protooncogene product. The predicted reading frame encoded a 1404-aa polypeptide that had the structure of a receptor-like protein-tyrosine kinase and exhibited the highest degree of sequence similarity with the Met/hepatocyte growth factor/scatter factor receptor. Analysis of steady-state RNA expression revealed that c-sea mRNA levels were elevated almost-equal-to 5-fold in chicken embryo cells transformed by activated variants of the src nonreceptor protein-tyrosine kinase gene but not in cells transformed by the nuclear oncogenes v-myc or v-rel A survey of c-sea expression in a variety of chicken tissues indicated that the highest levels of mRNA were located in peripheral white blood cell populations and in the intestine.