A soluble transforming growth factor-beta (TGF-beta ) type I receptor mimics TGF-beta responses.
Transforming growth factor-beta (TGF-beta) signaling requires a ligand-dependent interaction of TGF-beta receptors Tau beta R-I and Tau beta R-II. It has been previously demonstrated that a soluble TGF-beta type II receptor could be used as a TGF-beta antagonist. Here we have generated and investigated the biochemical and signaling properties of a soluble TGF-beta type I receptor (Tau beta RIs-Fc). As reported for the wild-type receptor, the soluble Tau beta R-I does not bind TGF-beta 1 on its own. Surprisingly, in the absence of TGF-beta1, the Tau beta RIs-Fc mimicked TGF-beta 1-induced transcriptional and growth responses in mink lung epithelial cells (Mv1Lu). Signaling induced by the soluble TGF-beta type I receptor is mediated via the obligatory presence of both TGF-beta type I and type II receptors at the cell surface since no signal was observed in Mv1Lu-derivated mutants for TGF-beta receptors R-1B and DR-26. The comparison between the structures of TGF-betas and a three-dimensional model of the extracellular domain of Tau beta RI has shown that five residues of the supposed binding site of TGF-beta 1 (Lys(31), His(34), Glu(5), Tyr(91), and Lys(94)) were found with equivalent biochemical properties and similar spatial positions.
Docagne
F
F
Université de Caen, UMR CNRS 6551, Centre Cyceron, IFR 47, Bd H. Becquerel, BP 5229, 14074 Caen Cedex, France.
Colloc'h
N
N
Bougueret
V
V
Page
M
M
Paput
J
J
Tripier
M
M
Dutartre
P
P
MacKenzie
E T
ET
Buisson
A
A
Komesli
S
S
Vivien
D
D
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002455:Cell Division / Q000502:physiology; D002460:Cell Line; D006224:Cricetinae; D017931:DNA Primers; D007074:Immunoglobulin G / Q000378:metabolism; D008907:Mink; D008969:Molecular Sequence Data; D011487:Protein Conformation; D018125:Receptors, Transforming Growth Factor beta / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D012995:Solubility; D016212:Transforming Growth Factor beta / Q000378:metabolism / Q000502:physiology*
D017931:DNA Primers; D007074:Immunoglobulin G; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta