Abstract
We have isolated the rat, mouse and human genes of a distant member of the TGF-beta superfamily, growth/differentiation factor-15/macrophage inhibiting cytokine-1 (GDF-15/MIC-1) by screening of genomic libraries. All three genes are composed of two exons, and contain one single intron that interrupts the coding sequences at identical positions within the prepro-domain of the corresponding proteins. The predicted proteins contain the structural hallmarks of members of the TGF-beta superfamily, including the seven conserved carboxy-terminal cysteine residues that form the cystine knot. The orthologous molecules show the lowest sequence conservation of all members of the TGF-beta superfamily. RT-PCR reveals an abundant expression of GDF-15/MIC-1 mRNA in numerous embryonic and adult organs and tissues. Promoter analysis of the rat promoter indicates the presence of multiple regulatory elements, including a TATA-like sequence as well as several SP1, AP-1 and AP-2 sites. Deletion analysis suggests that a 350 bp region upstream of the start of the open reading frame appears to be the most important for regulation of transcription.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Motifs
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Amino Acid Sequence
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Animals
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Cytokines / genetics*
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Cytokines / metabolism
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Gene Expression Regulation, Developmental*
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Growth Differentiation Factor 15
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Humans
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Mice
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Mice, Inbred BALB C
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Molecular Sequence Data
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Organ Specificity
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Promoter Regions, Genetic
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RNA, Messenger
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Rats
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Regulatory Sequences, Nucleic Acid
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Sequence Homology, Amino Acid
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Transforming Growth Factor beta / genetics
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Transforming Growth Factor beta / metabolism
Substances
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Cytokines
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GDF15 protein, human
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Gdf15 protein, mouse
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Gdf15 protein, rat
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Growth Differentiation Factor 15
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RNA, Messenger
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Transforming Growth Factor beta
Associated data
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GENBANK/AJ011967
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GENBANK/AJ011968
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GENBANK/AJ011969
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GENBANK/AJ011970
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GENBANK/AJ011971
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GENBANK/AJ011972
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GENBANK/AJ011973
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GENBANK/AJ011974
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GENBANK/AJ011975
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GENBANK/AJ011976
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GENBANK/AJ011977
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GENBANK/AJ011978
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GENBANK/AJ011979
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GENBANK/AJ011980
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GENBANK/AJ011981
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GENBANK/AJ011982
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GENBANK/AJ011983
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GENBANK/AJ011984
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GENBANK/AJ011985
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GENBANK/AJ011986
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GENBANK/AJ011987
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GENBANK/AJ011988
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GENBANK/AJ011989
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GENBANK/AJ011990
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GENBANK/AJ011991
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GENBANK/AJ011992
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GENBANK/AJ011993
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GENBANK/AJ011994
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GENBANK/AJ011995
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GENBANK/AJ011996