EXPRESSION AND MATURATION OF THE CELLULAR SEA RECEPTOR, A MEMBER OF THE HEPATOCYTE GROWTH-FACTOR (HGF) RECEPTOR FAMILY OF PROTEIN-TYROSINE KINASES

The c-sea proto-oncogene is a member of the Met/hepatocyte growth fact or/scatter factor family of receptor protein tyrosine kinases. A disti nguishing feature of this family, whose other member is the Ron/Stk re ceptor, is a novel heterodimeric structure. We have previously describ ed cDNA clones encoding the avian Sea receptor. In this report we show that a fun length c-sea cDNA directed the synthesis of a single 155 k Da polypeptide chain in vitro, while irt vivo two polypeptides of 160 and 180 kDa were observed. We analysed the structure of the Sea recept or using a soluble chimeric protein consisting of the Sea extracellula r domain linked to the hinge and constant regions of human IgG gamma 1 . These studies indicated that the receptor undergoes proteolytic proc essing in the extracellular domain yielding an approximate 35 kDa alph a and a 160 kDa beta chain, and thus the Sea receptor appears to displ ay a structure similar to that of the Met and Ron proteins. An examina tion of embryonic avian tissues using Sea extracellular domain-specifi c monoclonal antibodies revealed low levels of Sea receptor in a varie ty of tissues including kidney, intestine, liver, stomach, white blood cells and allantochorion. Elevated levels of expression were observed upon transformation of chicken embryo cells by the Src oncoprotein.