A WIDELY EXPRESSED TRANSMEMBRANE SERINE THREONINE KINASE THAT DOES NOT BIND ACTIVIN, INHIBIN, TRANSFORMING GROWTH-FACTOR-BETA, OR BONE MORPHOGENIC FACTOR

Molecular cloning of complementary DNAs (cDNA) whose expression produc ts bind activin and transforming growth factor beta (TGF-beta1 and -be ta2) 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 usin g degenerate oligonucleotide primers complementary to coding sequence for mouse activin and Caenorhabditis elegans daf-1 serine/threonine re ceptor kinase subdomains VI and VIII in the polymerase chain reaction. The deduced 509-amino acid product consisted of a cysteine-rich extra cellular 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 beta receptor kinases. Cells overexpre ssing SKR1 exhibited no increase in binding of activin, inhibin, TGF-b eta1, TGF-beta2, or bone morphogenic factor type 2B. Except for its ab sence in bone and spleen, SKR1 exhibits a tissue expression pattern si milar to the TGF-beta receptor II gene. Similarly, SKR1 is expressed i n normal parenchymal cells, endothelial cells, fibroblasts, and tumor- derived epithelial cells. The expression pattern and lack of binding t o proto-typic members of the TGF-beta1-5 branch of the TGF-beta superf amily suggests that SKR1 is potentially a receptor for a new member of the TGF-beta branch of the ligand superfamily.