Smad2 phosphorylation by type I receptor: contribution of arginine 462 and cysteine 463 In the C terminus of Smad2 for specificity
2004 (English)In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 279, no 34, 35781-35787 p.Article in journal (Refereed) Published
Transforming growth factor-beta (TGFbeta) is a potent regulator of cell proliferation, differentiation, motility, and apoptosis. TGFbeta binds to and activates serine/threonine kinase receptors that phosphorylate Smad2 and Smad3 intracellular signal transducers at two C-terminal serine residues. Here we show that substitutions of Arg-462 and Cys-463 residues, which are in proximity of the C-terminal serine residues, inhibited TGFbeta type I receptor-dependent phosphorylation of the C-terminal Smad2 peptides and full-length GST-Smad2 proteins in vitro. In vivo, mutation of Arg-462 and Cys-463 inhibited TGFbeta1-stimulated phosphorylation of the C-terminal serine residues in Smad2. Moreover, Smad2 with mutated Arg-462 and Cys-463 was less efficient in activation of the Smad2-responsive activin-responsive element-containing luciferase reporter ARE-luc, as compared with the wild-type protein. Thus, Arg-462 and Cys-463, which are in proximity of the C-terminal serine residues, contribute to recognition and phosphorylation of the C terminus of Smad2 by type I TGFbeta receptor.
Place, publisher, year, edition, pages
2004. Vol. 279, no 34, 35781-35787 p.
Activin Receptors; Type I/*metabolism, Amino Acid Substitution, Animals, Arginine, Binding Sites, COS Cells, Cercopithecus aethiops, Cysteine, DNA-Binding Proteins/*metabolism, Mice, Mutation, NIH 3T3 Cells, Phosphorylation, Protein Binding, Receptors; Transforming Growth Factor beta/*metabolism, Research Support; Non-U.S. Gov't, Substrate Specificity, Trans-Activators/*metabolism
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-72828DOI: 10.1074/jbc.M404377200PubMedID: 15210694OAI: oai:DiVA.org:uu-72828DiVA: diva2:100739