Identification and characterization of a novel follistatin-like protein as a binding protein for the TGF-β family

Kunihiro Tsuchida, Koji Y. Arai, Yoji Kuramoto, Norio Yamakawa, Yoshihisa Hasegawa, Hiromu Sugino

Research output: Contribution to journalArticle

151 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)40788-40796
Number of pages9
JournalJournal of Biological Chemistry
Volume275
Issue number52
DOIs
Publication statusPublished - 29-12-2000

Fingerprint

Follistatin
Activins
Carrier Proteins
Proteins
Bone Morphogenetic Protein 2
Follistatin-Related Proteins
Bone Morphogenetic Proteins
Cell signaling
Glutathione Transferase
Northern Blotting
Testis
Intercellular Signaling Peptides and Proteins
B-Lymphocytes
Fusion reactions
Complementary DNA
Cells

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Tsuchida, Kunihiro ; Arai, Koji Y. ; Kuramoto, Yoji ; Yamakawa, Norio ; Hasegawa, Yoshihisa ; Sugino, Hiromu. / Identification and characterization of a novel follistatin-like protein as a binding protein for the TGF-β family. In: Journal of Biological Chemistry. 2000 ; Vol. 275, No. 52. pp. 40788-40796.
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Identification and characterization of a novel follistatin-like protein as a binding protein for the TGF-β family. / Tsuchida, Kunihiro; Arai, Koji Y.; Kuramoto, Yoji; Yamakawa, Norio; Hasegawa, Yoshihisa; Sugino, Hiromu.

In: Journal of Biological Chemistry, Vol. 275, No. 52, 29.12.2000, p. 40788-40796.

Research output: Contribution to journalArticle

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