The L45 loop in type I receptors for TGF‐β family members is a critical determinant in specifying Smad isoform activation

FEBS Letters

Engström, Ulla¹  Grimsby, Susanne¹  Itoh, Susumu¹  Persson, Urban²  Heldin, Carl-Henrik¹  Izumi, Hiroto²  Souchelnytskyi, Serhiy¹  Funa, Keiko²  ten Dijke, Peter¹ 

[1] Ludwig Institute for Cancer Research, Box 595, SE-751 24 Uppsala, Sweden;Department of Anatomy and Cell Biology, Göteborg University, Box 420, SE-405 30 Göteborg, Sweden

关键词: Bone morphogenetic protein;    Receptor specificity;    Signal transduction;    Smad;    Transforming growth factor-β;   

DOI  :  10.1016/S0014-5793(98)00954-5

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Transforming growth factor-β (TGF-β) 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-β type I receptor (TβR-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 TβR-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.

【 授权许可】

Unknown