FEBS Letters · 1998 · 396 citations · 32 references
SclerostinL45 Loop RegionsOsteoporosisMolecular PharmacologySignaling PathwayBone Morphogenic ProteinCell SignalingMolecular SignalingMolecular PhysiologyG Protein-coupled ReceptorReceptor (Biochemistry)Smad Isoform ActivationCell BiologyMutant Bmpr-ibSignal TransductionDevelopmental BiologyTgf‐β Family MembersSystems BiologyMedicineL45 Loop
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.
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Mechanism of activation of the TGF-β receptor
Jeffrey L. Wrana, Liliana Attisano, Rotraud Wieser et al. · Nature · 1994 · 2.3K citations
Signal Transduction, Molecular Physiology, Tgf-β Receptor +6
Human Smad3 and Smad4 Are Sequence-Specific Transcription Activators
Leigh Zawel, Jia Le Dai, Phillip Buckhaults et al. · Molecular Cell · 1998 · 932 citations · Full text