A widely expressed transmembrane serine/threonine kinase that does not bind activin, inhibin, transforming growth factor β, orbone morphogenic factor

Molecular cloning of complementary DNAs (cDNA) whose expression products bind activin and transforming growth factor β (TGF-β1 and -β2) suggests that transmembrane serine/threonine kinases constitute a new class of signaling molecules. A human liver cell cDNA which codes for a new serine/threonine kinase receptor (SKR1) was identified using degenerate oligonucleotide primers complementary to coding sequence for mouse activin and Caenorhabditis elegans daf-1 serine/threonine receptor kinase subdomains VI and VIII in the polymerase chain reaction. The deduced 509-amino acid product consisted of a cysteine-rich extracellular domain and a cytoplasmic serine/threonine kinase domain which are 10-20 and 40% homologous to the respective domains in the activin and transforming growth factor β receptor kinases. Cells overexpressing SKR1 exhibited no increase in binding of activin, inhibin, TGF-β1, TGF-β2, or bone morphogenic factor type 2B. Except for its absence in bone and spleen, SKR1 exhibits a tissue expression pattern similar to the TGF-β receptor II gene. Similarly, SKR1 is expressed in normal parenchymal cells, endothelial cells, fibroblasts, and tumor-derived epithelial cells. The expression pattern and lack of binding to prototypic members of the TGF-β1-5 branch of the TGF-β superfamily suggests that SKR1 is potentially a receptor for a new member of the TGF-β branch of the ligand superfamily.