title: The L45 loop in type I receptors for TGF-beta family members is a critical determinant in specifying Smad isoform activation.
abstract: Transforming growth factor-beta (TGF-beta) and bone morphogenetic proteins (BMPs) signal via distinct type I and type II receptors and Smad proteins. A nine amino acid sequence between kinase subdomains IV and V in type I receptors, termed the L45 loop, has been shown to be important in conferring signalling specificity. We examined the responses of a mutant TGF-beta type I receptor (TbetaR-I) and a mutant BMPR-IB, in which the L45 regions of these two receptors were exchanged. Swapping the four amino acid residues that are different in BMPR-IB for those in TbetaR-I, and vice versa, switched their type I receptor-restricted Smad activation and specificity in transcriptional responses. These studies identify the L45 loop regions in type I receptors as critical determinants in specifying Smad isoform activation.
authors.affiliation: Department of Anatomy and Cell Biology, Göteborg University, Sweden.
authors.forename: U
authors.initials: U
authors.lastname: Persson
authors.forename: H
authors.initials: H
authors.lastname: Izumi
authors.forename: S
authors.initials: S
authors.lastname: Souchelnytskyi
authors.forename: S
authors.initials: S
authors.lastname: Itoh
authors.forename: S
authors.initials: S
authors.lastname: Grimsby
authors.forename: U
authors.initials: U
authors.lastname: Engström
authors.forename: C H
authors.initials: CH
authors.lastname: Heldin
authors.forename: K
authors.initials: K
authors.lastname: Funa
authors.forename: P
authors.initials: P
authors.lastname: ten Dijke
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D018125:Receptors, Transforming Growth Factor beta / Q000737:chemistry* / Q000378:metabolism*; D016415:Sequence Alignment; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D019485:Bone Morphogenetic Proteins; D004268:DNA-Binding Proteins; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta