GDF-3 and GDF-9: two new members of the transforming growth factor-beta superfamily containing a novel pattern of cysteines.
Two new mammalian members (growth/differentiation factor 3 (GDF-3) and GDF-9) of the transforming growth factor-beta superfamily were identified using degenerate oligonucleotides corresponding to conserved regions among known family members. By Northern analysis, GDF-3 transcripts were detected primarily in adult bone marrow, spleen, thymus, and adipose tissue. In contrast, GDF-9 transcripts were detected only in the ovary. Based on their cDNA sequences, the predicted GDF-3 and GDF-9 polypeptides each contain a potential signal sequence for secretion, a putative tetrabasic proteolytic processing site, and a COOH-terminal region that shows significant homology to the known members of the transforming growth factor-beta superfamily. In the COOH-terminal region, GDF-3 and GDF-9 are most homologous to Xenopus Vg-1 (57%) and human bone morphogenetic protein 4 (34%), respectively. Unlike all previously described members of this superfamily, both GDF-3 and GDF-9 lack the conserved cysteine residue that is believed to form the sole disulfide linkage between subunits in other family members. These findings raise new possibilities regarding subunit interactions among members of this superfamily.
McPherron
A C
AC
Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Lee
S J
SJ
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D055430:Bone Morphogenetic Protein 15; D003545:Cysteine; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D005260:Female; D055451:Growth Differentiation Factor 3; D055429:Growth Differentiation Factor 9; D006133:Growth Substances / Q000235:genetics*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D005810:Multigene Family; D009838:Oligodeoxyribonucleotides; D009928:Organ Specificity; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D016212:Transforming Growth Factor beta / Q000235:genetics*; D014981:Xenopus
C525901:BMP15 protein, human; C525902:Bmp15 protein, mouse; D055430:Bone Morphogenetic Protein 15; C525974:GDF3 protein, human; C525897:GDF9 protein, human; C525975:Gdf3 protein, mouse; C525898:Gdf9 protein, mouse; D055451:Growth Differentiation Factor 3; D055429:Growth Differentiation Factor 9; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D004247:DNA; D003545:Cysteine