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

FEBS Lett. 1998 Aug 28;434(1-2):83-7. doi: 10.1016/s0014-5793(98)00954-5.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Bone Morphogenetic Proteins / metabolism*
  • DNA-Binding Proteins / metabolism*
  • Molecular Sequence Data
  • Receptors, Transforming Growth Factor beta / chemistry*
  • Receptors, Transforming Growth Factor beta / metabolism*
  • Sequence Alignment
  • Signal Transduction*
  • Transforming Growth Factor beta / metabolism*


  • Bone Morphogenetic Proteins
  • DNA-Binding Proteins
  • Receptors, Transforming Growth Factor beta
  • Transforming Growth Factor beta