The L45 loop in type I receptors for TGF-beta family members is a critical determinant in specifying Smad isoform activation.
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.
Persson
U
U
Department of Anatomy and Cell Biology, Göteborg University, Sweden.
Izumi
H
H
Souchelnytskyi
S
S
Itoh
S
S
Grimsby
S
S
Engström
U
U
Heldin
C H
CH
Funa
K
K
ten Dijke
P
P
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*
D019485:Bone Morphogenetic Proteins; D004268:DNA-Binding Proteins; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta