TY - JOUR
T1 - Identification and characterization of a novel follistatin-like protein as a binding protein for the TGF-β family
AU - Tsuchida, Kunihiro
AU - Arai, Koji Y.
AU - Kuramoto, Yoji
AU - Yamakawa, Norio
AU - Hasegawa, Yoshihisa
AU - Sugino, Hiromu
PY - 2000/12/29
Y1 - 2000/12/29
N2 - Follistatin is an activin-binding protein that prevents activin from binding to its receptors and neutralizes its activity. Follistatin also binds bone morphogenetic proteins (BMPs). In this study, we report the identification of a novel follistatin-like protein from mouse. The mouse cDNA encodes a 256-residue precursor and most likely a mouse homologue of human FLRG, which was found at the breakpoint of the chromosomal rearrangement in a B-cell line. Whereas follistatin has three follistatin domains, which are presumed to be growth factor binding motifs, FLRG possesses only two follistatin domains. Northern blotting revealed that mRNAs for FLRG were abundantly expressed in heart, lung, kidney, and testis in mouse. The recombinant mouse FLRG proteins were found to have binding activity for both activin and bone morphogenetic protein-2. Like follistatin, FLRG has higher affinity for activin than for BMP-2. The FLRG protein inhibited activin-induced and BMP-2-induced transcriptional responses in a dose-dependent manner. Glutathione S-transferase fusion proteins encoding various regions of FLRG were produced and studied. Ligand blotting using 125I-activin revealed that the COOH-terminal region containing the second follistatin domain was able to bind activin. Our finding implies that cellular signaling by activin and BMPs is tightly regulated by multiple members of the follistatin family.
AB - Follistatin is an activin-binding protein that prevents activin from binding to its receptors and neutralizes its activity. Follistatin also binds bone morphogenetic proteins (BMPs). In this study, we report the identification of a novel follistatin-like protein from mouse. The mouse cDNA encodes a 256-residue precursor and most likely a mouse homologue of human FLRG, which was found at the breakpoint of the chromosomal rearrangement in a B-cell line. Whereas follistatin has three follistatin domains, which are presumed to be growth factor binding motifs, FLRG possesses only two follistatin domains. Northern blotting revealed that mRNAs for FLRG were abundantly expressed in heart, lung, kidney, and testis in mouse. The recombinant mouse FLRG proteins were found to have binding activity for both activin and bone morphogenetic protein-2. Like follistatin, FLRG has higher affinity for activin than for BMP-2. The FLRG protein inhibited activin-induced and BMP-2-induced transcriptional responses in a dose-dependent manner. Glutathione S-transferase fusion proteins encoding various regions of FLRG were produced and studied. Ligand blotting using 125I-activin revealed that the COOH-terminal region containing the second follistatin domain was able to bind activin. Our finding implies that cellular signaling by activin and BMPs is tightly regulated by multiple members of the follistatin family.
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U2 - 10.1074/jbc.M006114200
DO - 10.1074/jbc.M006114200
M3 - Article
C2 - 11010968
AN - SCOPUS:0034731508
SN - 0021-9258
VL - 275
SP - 40788
EP - 40796
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 52
ER -