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 products bind activin and transforming growth factor beta (TGF-beta 1 and -beta 2) 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 beta receptor kinases. Cells overexpressing SKR1 exhibited no increase in binding of activin, inhibin, TGF-beta 1, TGF-beta 2, or bone morphogenic factor type 2B. Except for its absence in bone and spleen, SKR1 exhibits a tissue expression pattern similar to the TGF-beta 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-beta 1-5 branch of the TGF-beta superfamily suggests that SKR1 is potentially a receptor for a new member of the TGF-beta branch of the ligand superfamily.
W. Alton Jones Cell Science Center, Inc., Lake Placid, New York 12946.
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Matsuzaki
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Xu
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Wang
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McKeehan
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Krummen
M
M
Kan
D028341:Activins; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D019485:Bone Morphogenetic Proteins; D006528:Carcinoma, Hepatocellular; D002460:Cell Line; D003001:Cloning, Molecular; D004273:DNA, Neoplasm; D015870:Gene Expression; D006133:Growth Substances / Q000378:metabolism*; D006801:Humans; D007265:Inhibins / Q000378:metabolism; D008099:Liver / Q000201:enzymology*; D008113:Liver Neoplasms; D008969:Molecular Sequence Data; D009036:Moths; D009838:Oligodeoxyribonucleotides; D016133:Polymerase Chain Reaction; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D012334:RNA, Neoplasm / Q000302:isolation & purification / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014407:Tumor Cells, Cultured
D019485:Bone Morphogenetic Proteins; D004273:DNA, Neoplasm; D006133:Growth Substances; D009838:Oligodeoxyribonucleotides; D011506:Proteins; D012334:RNA, Neoplasm; D016212:Transforming Growth Factor beta; D028341:Activins; D007265:Inhibins; D017346:Protein Serine-Threonine Kinases