Using degenerate primers designed against a peptide purified from a rat glioma cell line, Zwijsen et al. (1994) isolated
a full-length follistatin-like cDNA (FSTL1), which they called FRP, from a human glioma cDNA library. FSTL1
encodes a deduced 308-amino acid protein with an N-terminal signal peptide of 20 amino acids. FSTL1 contains an FS
module, a follistatin-like sequence containing 10 conserved cysteine residues.
NCBI Summary:
This gene encodes a protein with similarity to follistatin, an activin-binding protein. It contains an FS module, a follistatin-like sequence containing 10 conserved cysteine residues. This gene product is thought to be an autoantigen associated with rheumatoid arthritis.
General function
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Cellular localization
Nuclear
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Ovarian function
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Using Northern blot
analysis, Tanaka et al. (1998) detected a broadly expressed 4.4-kb FSTL1 transcript most strongly in the heart,
placenta, prostate, ovary, and small intestine.
Expression regulated by
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Ovarian localization
Granulosa, Theca
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Tortoriello DV, et al 2001 reported the identification of human follistatin-related protein,a structural homologue of follistatin with nuclear localization.
Follistatin-related protein, like
follistatin, preferentially bound activin with high affinity and in an
essentially irreversible fashion. Although follistatin-related protein, like
follistatin, possesses a signal sequence and no known nuclear localization
signals, its secretion was undetectable in most cell lines by RIA.
Intriguingly, follistatin-related protein was identified as a nuclear protein
in human granulosa cells and all human cell lines tested. Furthermore, Western
analyses of CHO cells transfected with human follistatin-related protein
revealed this protein to reside within the insoluble nuclear protein fraction.
Follicle stages
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Liu J, et al reported the regulation of follistatin-related gene (FLRG) expression by
protein kinase C and prostaglandin E-2 in cultured
granulosa-luteal cells.
The recently identified
follistatin-related gene (FLRG) is expressed abundantly in the human ovary,
has high affinity for activin, and is able to inhibit activin-induced
transcriptional responses. However, little is known about the regulation of
FLRG expression in specific cell types in the ovary, while it is known that
gonadotrophins induce follistatin gene expression in human granulosaluteal
cells. In this study, the authprs investigated the expression of FLRG mRNA in
granulosa-luteal cells of preovulatory follicles obtained from women
undergoing IVF. FLRG mRNA was detected by RT-PCR in fresh and cultured
granulosa-luteal cells, as well as in normal ovarian stroma, theca and
granulosa cells. Northern blot analysis revealed a 2.5 kb transcript of the
FLRG in cultured granulosa-luteal cells. The protein kinase C activator,
12-O-tetradecanoyl phorbol 13-acetate (TPA, 160 nmol/l), and prostaglandin E-2
(PGE(2), 1 mumol/l) increased FLRG mRNA accumulation up to 3-8 fold over the
control level after 24 h of treatment, and these stimulatory effects were
dose-dependent. Co-treatment with the protein kinase C inhibitor, Ro-31-8220
(3 mumol/l), blocked the stimulatory effect of TPA. Although short term
treatment with the protein kinase A activator, (Bu)(2)cAMP (1 mmol/l),
slightly reduced FLRG mRNA expression in most experiments, long term treatment
with FSH (100 IU/l), LH (100 IU/I), or (Bu)(2)cAMP had no significant effect
on the FLRG mRNA levels. As expected, gonadotrophins, protein kinase A and C
activators and PGE(2) increased granulosa-luteal cell progesterone secretion
into the culture media. Taken together, previous and our present data suggest
that protein kinase C and A signal transduction pathways differently regulate
the expression of FLRG and follistatin genes in human ovarian granulosa-luteal
cells.