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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recombinant expression of human alpha- and beta A-inhibin subunit cDNAs in mammalian 293 cells results in the secretion of 20-53K free alpha-subunit-derived products, 30-105K alpha beta A-inhibin dimers, and 24-110K beta A-activin dimers. The present study verifies that the wide variation in the size of these products is due to incomplete cleavage of the proteolytic processing sites and the differential glycosylation of the N-linked glycosylation site at amino acid number 302 in the alpha C-subunit. The identity of each of these products was established by mutagenesis of proteolytic processing sites and N-linked glycosylation sites, combined with the analysis of transfection products by immunoprecipitation and one- and two-dimensional SDS-PAGE (SDS/SDS-beta-ME). Transient expression of processing site mutants of the alpha- and beta A-subunits in 293 cells was used to generate microgram quantities of noncleavable 55K and 65K inhibin dimers, and noncleavable 110K activin A dimers. The 55K and 65K inhibin A forms were purified and found to be fully biologically active in a rat pituitary cell bioassay. The 110K high molecular weight (HMW) form of human activin A failed to show any FSH-releasing activity in the pituitary assay. Since radioactively labeled 55K and 65K inhibin A and 110K activin A remained intact after incubation with rat pituitary cells for 72 h, there appears to be no conversion of these dimers to lower molecular weight forms by proteolytic cleavage at additional sites. These results show for the first time that 55K and 65K inhibit A are intrinsically biologically active and do not require cleavage to the 32K form for activation. In contrast, cleavage of the 110K activin A precursor to the 24K form would appear to be necessary for activity.
Mol Endocrinol 1996 Sep
PMID:Characterization and determination of the biological activities of noncleavable high molecular weight forms of inhibin A and activin A. 888 40

A role for activin in the acquisition of gonadotropin responsiveness by the post-natal rat ovary was investigated. The inhibin/activin subunits in terms of protein and mRNA, were localised in granulosa cells of the rat ovary at days 4, 8 and 12 after birth. A characteristic pattern of responses to FSH for inhibin and progesterone (P) production was established using a dispersed ovarian cell bioassay. P production by day 4, 8 and 12 cultures was stimulated by FSH, but only when iso-butyl-methyl-xanthine (MIX) was present. In contrast, a basal level of inhibin production was measured in day 4 cultures which was not responsive to FSH or MIX. In day 8 and 12 cultures, inhibin production was FSH-responsive, but only in the absence of MIX. The addition of activin to cultures of day 4, 8 and 12 ovarian cells induced FSH-responsive P production and stimulated both basal and FSH-stimulated inhibin production. These studies indicate a differential response of neonatal ovarian cells to FSH in terms of P and inhibin production. Activin may play a role in facilitating the effects of FSH on signal transduction pathways leading to inhibin and steroid production and therefore be part of the mechanism which determines responsiveness of granulosa cells to FSH.
Mol Cell Endocrinol 1996 Aug 30
PMID:Differential responses of post-natal rat ovarian cells to FSH and activin. 889 45

The effects of recombinant human activin A on the development of bovine one-cell embryos matured and fertilized in vitro were investigated. In experiment 1, one-cell embryos were cultured in a chemically-defined medium, of modified synthetic oviduct fluid supplemented with 1 mg/ml polyvinyl alcohol (mSOF-PVA), containing different concentrations of activin (0, 0.1, 1, 10, and 100 ng/ml) until 240 hr after in vitro fertilization. The addition of > or = 1 ng/ml activin to mSOF-PVA improved development to the blastocyst stage (14.5-17.1%), compared with no addition of activin (5.6%). However, there was no significant difference in hatching rate of embryos among treatments. In experiments 2 and 3, the embryos were also cultured in mSOF-PVA at various periods of exposure to 10 ng/ml activin, to evaluate development to the morula and blastocyst stages, respectively. The proportion of morulae was significantly higher in culture with activin at 20-120 hr postinsemination (37.2%) than with control (25.7%). Total number of cells in morulae at 120 hr postinsemination significantly increased by the addition of activin at 20-72 hr (26.1 cells) and 20-120 hr (24.2 cells) postinsemination, compared with control (20.1 cells). When activin was added to the medium during 20-120 hr and 20-192 hr postinsemination, the percentages of blastocysts (18.0% and 18.7%, respectively) were significantly higher than in the control (9.6%). However, the total number of cells in blastocysts was not significantly different. These results demonstrate that activin stimulates the development of bovine one-cell embryos to the morula and blastocyst stages in vitro.
Mol Reprod Dev 1996 Oct
PMID:Recombinant human activin A stimulates development of bovine one-cell embryos matured and fertilized in vitro. 891 72

A cDNA clone encoding a new member of the type I serine/threonine kinase receptors of the TGF-beta/BMP superfamily was isolated from a rat prostate cDNA library. The predicted sequence of the encoded protein is 493 amino acids with a molecular weight of 55 kDa. It contains a putative cysteine rich extracellular domain, a transmembrane domain, a conserved type I receptor GS domain and a cytoplasmic serine/threonine kinase domain. The kinase domain shares 80% homology with that of ALK-4 and ALK-5 whose ligands are activin and TGF-beta. Northern blot analysis revealed that this prostate serine/threonine kinase receptor I (PSKR-I) is highly expressed in rat dorsolateral prostate, coagulating gland (anterior prostate), cerebellum and adipose tissue.
Biochem Mol Biol Int 1996 Nov
PMID:Identification and cloning of a novel type I serine/threonine kinase receptor of the TGF-beta/BMP superfamily in rat prostate. 895 89

The localizations of serine-threonine kinase receptor mRNA for the novel type I TGF-beta and/or activin receptor named B1 (rat), ALK-4 (mouse) or ActR-IB (human) were demonstrated by in situ hybridization. As the putative ligand for this receptor in the brain has not yet been clearly determined, we compared its localization to type II activin receptor (ActR-II) which is the counterpart of the type I activin receptor. B1 mRNA was widely observed in neuronal cells throughout the brain, and especially strong positive signals were found in the cerebral cortex, olfactory tubercle, and hippocampus. The localization of B1 mRNA coincided well with that of ActR-II. This strongly suggests that B1 (ALK-4/ActR-IB) could be the type I activin receptor, as type I and type II activin receptor were supposed to form a receptor complex. In addition, we examined the localization of type II TGF-beta receptor (TbetaRII) mRNA which is an essential counterpart of the type I TGF-beta receptors for TGF-beta signaling. TbetaRII mRNA was expressed mainly in non-neuronal cells such as choroid plexus. In addition, TbetaRII mRNA expression was also found in a minor population of neuronal cells. TbetaRII mRNA-positive neurons were observed in the reticular thalamus, laterodorsal tegmental nucleus, pedunculopontine tegmental nucleus and the ventral tegmental nucleus. The localization of TbetaRII was markedly different from that of activin receptors in the rat brain. Since TGF-betas and activins are known as growth factors and/or survival factors, we examined changes in levels of B1 and TbetaRII mRNA expression during peripheral nerve regeneration. Expression of B1 mRNA in the axotomized hypoglossal motoneurons was substantially decreased from day 3 after axotomy and this decrease was significant until postoperative day 28, whereas no TbetaRII signal was observed in hypoglossal nucleus prior or after axotomy. This transient down-regulation of B1 mRNA expression suggests that activin signaling is somehow suppressed during peripheral nerve regeneration.
Brain Res Mol Brain Res 1996 Dec
PMID:Distinct localization of two serine-threonine kinase receptors for activin and TGF-beta in the rat brain and down-regulation of type I activin receptor during peripheral nerve regeneration. 901 82

Activins and inhibins belong to the transforming growth factor beta (TGF-beta)-like superfamily and exert their effects on a broad range of cellular targets by modulating cell differentiation and proliferation. Members of this family interact with two structurally related classes of receptors (type I and type II), both containing a serine/threonine kinase domain. When expressed alone, the type II but not the type I activin receptor can bind activin. However, the presence of a type I receptor is required for signaling. For TGF-beta1, ligand binding to the type II receptor results in the recruitment and transphosphorylation of the type I receptor. Transient overexpression of the two types of activin receptor results in ligand-independent receptor heteromerization and activation. Nevertheless, activin addition to the transfected cells increased complex formation between the two receptors, suggesting a mechanism of action similar to that observed for the TGF-beta receptor. In the present study, we generated a stable cell line, overexpressing the two types of activin receptor upon induction, in the human erythroleukemia cell line K562. We demonstrate here that activin specifically induces heteromer formation between the type I and type II receptors in a time-dependent manner. Using this stable line, we analyzed the effects of activin and inhibin on human erythroid differentiation. Our results indicate that activin signal transduction mediated through its type I and type II receptors results in an increase in the hemoglobin content of the cells and limits their proliferation. Finally, using cell lines that can be induced to overexpress ActRII and ActRIB or ActRIB only, we show that the inhibin antagonistic effects on activin-induced biological responses are mediated through a competition for the type II activin receptor but also require the presence of an inhibin-specific binding component.
Mol Cell Biol 1997 Mar
PMID:Activin and inhibin have antagonistic effects on ligand-dependent heteromerization of the type I and type II activin receptors and human erythroid differentiation. 903 95

As a first step towards providing a conceptual approach to understanding similarities and differences in the mechanisms which guide inductive interactions among related organisms (e.g. various amphibia), a set of five principles is offered here. These principles were formulated by analyzing literature examples of classical embryological phenomena and by performing experiments with activin, a peptide growth factor which is currently suspected to play for a role in mesoderm induction. Mechanisms which account, at least in part, for the observed differences between anuran and urodele inductive processes can be derived from these principles.
Cell Mol Life Sci 1997 Apr
PMID:An essay on the similarities and differences between inductive interactions in anuran and urodele embryos. 913 29

The expression of both inhibin alpha- and inhibin/activin beta A-subunit mRNA was examined in equine uteroplacental tissues collected during pregnancy (days 90 to 300). Northern blot analysis revealed that 5 transcripts (7.0, 4.1, 3.4, 2.6, 1.5 kb) of beta A-subunit were present, and the most abundantly expressed transcript was the 1.5 kb one. Relatively high levels of the 1.5 kb transcript were seen in the second trimester of pregnancy compared to what was found in the third trimester. To identify the tissue localization of beta A-subunit mRNA, in situ hybridization was performed, and the positive signal was observed exclusively in the endometrial glands, but not in the fetal placental tissue (trophoblast) at days 150, 210, and 300 of pregnancy. On the other hand, inhibin alpha-subunit transcript could not be detected at any stage of pregnancy examined either by Northern blot analysis or in situ hybridization. Although the factor(s) regulating the gene expression of beta A-subunit in this equine tissue is currently unknown, these results suggest that activin, but not inhibin, is predominantly produced in the endometrial glands of the pregnant mare, and thus produced activin may play a paracrine or endocrine role during pregnancy in this species.
Mol Reprod Dev 1997 Aug
PMID:Equine inhibin/activin beta A-subunit mRNA is expressed in the endometrial gland, but not in the trophoblast, during pregnancy. 921 20

We have cloned a full length cDNA coding for activin beta B subunit from the goldfish ovary. Sequence analysis of the goldfish activin beta B shows that this peptide is extremely conserved across vertebrates. The mature region of goldfish activin beta B has 93 and 98% amino acid identity with that of human and zebrafish beta B subunit respectively. The identity of the cloned goldfish activin beta B was further confirmed by expressing the protein in the Chinese hamster ovary (CHO) cells followed by detection of the specific activity of activin in the culture medium using F5-5 cell assay. mRNA of goldfish activin beta B is expressed in a variety of goldfish tissues including ovary, testis, brain, pituitary, kidney and liver, suggesting a wide range of physiological roles for activin in the goldfish.
J Mol Endocrinol 1997 Aug
PMID:Cloning of cDNA for goldfish activin beta B subunit, and the expression of its mRNA in gonadal and non-gonadal tissues. 927 59

We have cloned a full length cDNA coding for the activin type IIB receptor (GactRIIB) from the goldfish ovary. GactRIIB shares 73 and 70% amino acid identity in the extracellular domain, and 78 and 80% identity in the intracellular domain with the type IIB receptors of the mouse and Xenopus respectively. The intracellular domain of GactRIIB contains two serine kinase consensus sequences, DFKSRN and GTRRYMAPE, in agreement with the reports in other vertebrates that serine/threonine phosphorylation is involved in activin signal transduction. The identity of GactRIIB was confirmed by transient expression in the COS cells followed by activin binding. Iodinated human activin A bound to the GactRIIB-transfected cells and the binding could be completely inhibited by unlabeled activin. Affinity labeling revealed a band of about 85 kDa, which is in agreement with the reported type II receptors in other vertebrates. Together with the fact that activin is expressed in the goldfish ovary, the cloning of activin receptors from the ovary suggests paracrine and autocrine roles for activin in the goldfish ovarian functions.
J Mol Endocrinol 1997 Aug
PMID:Cloning and characterization of goldfish activin type IIB receptor. 927 60


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