The GS domain of the transforming growth factor-beta type I receptor is important in signal transduction.
Signal transduction by transforming growth factor-beta (TGF-beta) involves the formation of a heteromeric complex of two transmembrane serine/threonine kinase receptors, type I (T beta R-I) and type II (T beta R-II). In the region preceeding the kinase domain of T beta R-I there is a glycine- and serine-rich sequence, termed the GS domain, which has been shown to be phosphorylated by T beta R-II. In order to determine the importance of the serine residues in this domain, receptor mutants with one or more serine residues mutated were analyzed. All the mutants of T beta R-I were able to bind ligand and their kinase activity was not abolished by the mutations. The receptor mutants with single mutated serine residues mediated transcriptional responses to TGF-beta with similar efficiency as the wild type receptor, whereas those with two or three of the serine residues mutated showed only weak transcriptional responses. These results suggest that serine residues in the GS domain are important for signal transduction by T beta R-I; however, the signaling activity of T beta R-I does not depend on any particular serine residue in the GS domain, but rather on how many of the serine residues in the region are intact.
Franzén
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Ludwig Institute for Cancer Research, Biomedical Center, Uppsala, Sweden.
Heldin
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CH
Miyazono
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D030201:Activin Receptors, Type I; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002522:Chlorocebus aethiops; D003432:Cross-Linking Reagents; D005998:Glycine; D006801:Humans; D007668:Kidney; D008168:Lung; D008907:Mink; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis / Q000378:metabolism; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000096:biosynthesis / Q000502:physiology*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism / Q000494:pharmacology; D012694:Serine; D015398:Signal Transduction; D013388:Succinimides / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D003432:Cross-Linking Reagents; D018125:Receptors, Transforming Growth Factor beta; D011994:Recombinant Proteins; D013388:Succinimides; D016212:Transforming Growth Factor beta; D012694:Serine; D017346:Protein Serine-Threonine Kinases; D030201:Activin Receptors, Type I; D000077293:Receptor, Transforming Growth Factor-beta Type I; D005998:Glycine; C019358:disuccinimidyl suberate