Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Of TGF-beta superfamily proteins, BMP-2 enhanced alkaline phosphatase (ALP) activity in cultured osteoblastic cells, MC3T3-E1, to the same level promoted by ascorbate, whereas TGF-beta s (beta 1, beta 2, beta 3) reduced ALP activity and altered cell morphology under the same conditions. Activin appeared to have no distinct effect on ALP synthesis. Ascorbate dependent increase in ALP synthesis was markedly stimulated in the presence of BMP-2. The synergistic effect of ascorbate on ALP synthesis was replaced by type I collagen coated on the culture dish. However, BMP-2 appeared not to bind to type I collagen. These findings indicate that BMP-2 acts directly on osteoblastic cells through its receptors and collagenous matrix can neither recruit BMP-2 nor modulate directly the action of BMP-2 in the pericellular area. Treatment of cells grown in ascorbate media with TGF-beta s decreased rapidly the cellular ALP activity indicating that TGF-beta s direct cells to the dedifferentiated stage.
Mol Cell Biochem 1996 Dec 06
PMID:Synergistic effect of BMP-2 and ascorbate on the phenotypic expression of osteoblastic MC3T3-E1 cells. 897 78

Activin A, a member of the transforming growth factor beta (TGF-beta) superfamily, is a protein consisting of two homodimeric beta A subunits. It was originally isolated from follicular fluid as a factor stimulating the release of follicle-stimulating hormone from the pituitary gland. Increasing evidence suggests that activin A is broadly distributed and regulates multiple functions in various biological systems by autocrine/paracrine mechanisms. In this review, we discuss the effects of activin A on hematopoiesis, especially the enhancement of erythropoiesis, and the production of activin A within the bone marrow microenvironment and in peripheral blood monocytes. The regulatory control of activin A expression by its 5' promoter region is also discussed. Furthermore, we consider that the expression of activin A is modulated by different agents, including proinflammatory cytokines, glucocorticoids and retinoic acid, suggesting new roles for activin A in inflammation reactions. Recently, this role in inflammation was further strengthened by the findings that activin A expression is elevated in inflammatory arthropathies, is regulated by inflammation-associated cytokines in synoviocyte and articular chondrocyte cultures, and is able to counteract many of the interleukin-6 (IL-6)-induced biological activities. Therefore it is likely that activin A may also act as a paracrine/autocrine moderator in diverse functions, including host defenses.
Cytokines Cell Mol Ther 1997 Sep
PMID:Production of activin A and its roles in inflammation and hematopoiesis. 942 75

The aim of this study was to investigate whether bovine cumulus-oocyte complexes (COCs) synthesize activin A, inhibin, and follistatin and whether they contain activin receptor during in vitro maturation. Therefore, COCs obtained from small and medium-sized follicles were cultured in M-199 supplemented with 10% fetal calf serum (FCS) and gonadotropins for 24 hr. At 0, 6, 12, and 24 hr after the onset of culture, COCs were removed for immunohistochemical staining to detect the expression of activin A, inhibin, follistatin, and activin receptor type II proteins. At 0 and 24 hr, COCs were removed and prepared for reverse-transcriptase polymerase chain reaction (RT-PCR) to assess the presence of mRNA of these proteins. It appeared that cumulus cells and oocytes express activin, follistatin, and activin receptor proteins as well as their mRNA. While expression of inhibin mRNA was found exclusively in cumulus cells, the inhibin protein was present in cumulus cells and oocytes. Immunohistochemical study both in cumulus cells and in oocytes often showed a moderate and strong staining intensity for activin and follistatin, respectively. Activin staining underwent little or no change during culture except at 24 hr of maturation, where about 60% of the oocytes showed no staining. Follistatin immunoreactivity remained strong in the majority of COCs. At the onset of culture, a spotlike inhibin staining was observed in the oocyte, which increased after 12 hr and was absent at the end of culture. Activin receptor immunoreactivity in cumulus cell membranes and oolemma increased during oocyte maturation to maximum values at the end of culture in most of the COCs. It is concluded that the consistent presence of activin and the increase in activin receptor in cumulus cells and oocytes during in vitro maturation indicate a paracrine and/or autocrine action for activin on bovine oocyte maturation. This action may be modulated by inhibin and/or follistatin.
Mol Reprod Dev 1998 Feb
PMID:Immunohistochemical localization and mRNA expression of activin, inhibin, follistatin, and activin receptor in bovine cumulus-oocyte complexes during in vitro maturation. 944 61

Using a Xenopus expression-cloning screen, we have isolated Gremlin, a novel antagonist of bone morphogenetic protein (BMP) signaling that is expressed in the neural crest. Gremlin belongs to a novel gene family that includes the head-inducing factor Cerberus and the tumor suppressor DAN. We show that all family members are secreted proteins and that they act as BMP antagonists in embryonic explants. We also provide support for the model that Gremlin, Cerberus, and DAN block BMP signaling by binding BMPs, preventing them from interacting with their receptors. In addition, Cerberus alone blocks signaling by Activin- and Nodal-like members of the TGF beta superfamily. Therefore, we propose that Gremlin, Cerberus, and DAN control diverse processes in growth and development by selectively antagonizing the activities of different subsets of the TGF beta ligands.
Mol Cell 1998 Apr
PMID:The Xenopus dorsalizing factor Gremlin identifies a novel family of secreted proteins that antagonize BMP activities. 966 Sep 51

Whisker pad innervation and whisker-specific pattern formation were examined in mice lacking the gene for activin betaA or for follistatin. Both strains of mice die within 24 h after birth. A normal array of whisker follicles is present in the snout of either phenotype. However, activin betaA-deficient mice lack whiskers, and in follistatin-deficient mice the whiskers are thin and curled. We examined the effects of aberrant, albeit innervated, follicles on the formation of whisker-specific patterns (barrelettes) in the trigeminal brainstem. Activin betaA knockout mice lack barrelettes, although the trigeminal afferent topography is not compromised. Physiological recordings suggest that trigeminal ganglion cells in these mice are less responsive to stimulation of whisker follicles. Barrelettes in follistatin-deficient mice are not as well developed as in controls, but can be discerned in some cases. These results are consistent with the notion that formation of barrelettes depends on neural activity initiated by the whiskers.
Mol Cell Neurosci 1998 Nov
PMID:Defective whisker follicles and altered brainstem patterns in activin and follistatin knockout mice. 982 86

Activin, and its binding protein, follistatin, are up-regulated by mediators of inflammation, and recent studies have demonstrated that activin A can block the activity of the key inflammatory cytokine, interleukin-6 (IL-6). These findings thereby implicate activin and follistatin in the control of the inflammatory cascade. In this study, interactions between interleukin-1beta (IL-1beta), IL-6 and activin were examined the human liver cell line, HepG2, for their effect on cell proliferation and the production of the acute phase proteins, haptoglobin and alpha1-acid glycoprotein (alpha1-AGP). IL-1beta and activin A, but not IL-6, inhibited the proliferation of HepG2 cells. Activin A together with IL-1beta caused a greater inhibition of proliferation than either factor alone, and the inhibitory effects of activin A were blocked by the addition of follistatin to the cultures. Activin A alone inhibited the production of haptoglobin but did not affect alpha1-AGP concentrations. However, activin A suppressed the stimulatory effects of IL-6 on the production of both haptoglobin and alpha1-AGP. Production of follistatin by HepG2 cells was stimulated by activin A, but was inhibited by both IL-1beta and IL-6, indicating a complex regulatory loop is operable to modulate the effects of activin A during inflammation. Taken together, these data suggest that activin A interacts with IL-1beta and IL-6 to regulate and coordinate the production of acute phase proteins during an inflammatory episode.
Mol Cell Endocrinol 1999 Feb 25
PMID:Activin A regulates growth and acute phase proteins in the human liver cell line, HepG2. 1022 78

Activin uptake into Xenopus oocytes was studied by several complementary methods. Immunocytochemistry of adult ovary localized activin and follistatin in the cytoplasm of vitellogenic oocytes and surrounding follicle cells. Surface plasmon resonance analysis of protein interaction kinetics indicated that while follistatin or a complex of activin-follistatin bound to yolk vitellogenin, activin alone did not. Radioactive tracer analysis measured specific incorporation of activin by viable oocytes in vitro. Together, the results suggest that vitellogenic oocytes can import activins from follicle cells and that follistatin may act as a chaperone for binding activin to vitellogenin in yolk platelets.
Cell Mol Biol (Noisy-le-grand) 1999 Jul
PMID:Activin incorporation into vitellogenic oocytes of Xenopus laevis. 1051 87

The primary patterning event in early vertebrate development is the formation of mesoderm and subsequent induction of the neural tube by the mesoderm. Some of the transforming growth factor (TGF)-beta family (Activin, Vg1) and the fibroblast growth factor (FGF) family molecules have been implicated for their roles in mesoderm induction. Here we show first the evidence that neuregulin, an epidermal growth factor (EGF)-like growth factor known for its role in neural and muscle differentiation, participates in mesoderm induction. Neuregulin could induce the ectopic expression of mesoderm specific gene Xbra in animal cap explants reared to the midgastrula stage, when animal caps dissected from late blastula were cultured with Neuregulin at a low concentration (10 ng/ml). In situ hybridization study showed that alpha-cardiac actin was expressed in animal caps that were treated with Neuregulin overnight. Skeletal and cardiac muscle specific genes such as MyoD family genes (myoD, MRF4, myf5) and SL1 as well as NCAM, a pan neural marker, were also ectopically expressed by treatment with Neuregulin. However, the expression of NCAM is presumed to be a secondary result of the initial mesoderm induction by Neuregulin. The temporal expression pattern of neuregulin during the early developmental stages was analyzed by RT-PCR in order to determine if neuregulin is expressed at the time of mesoderm induction. It has been found that the neuregulin transcript was already detected from the 16-cell stage (stage 5) and continued to be expressed till the tailbud stage (stage 25), the latest embryonic stage analyzed in this study. Considering that the mesoderm is induced at early blastula before the start of zygotic transcription, maternal neuregulin is expressed at the right time to participate in mesoderm induction. These data strongly suggest that neuregulin plays an important role in mesoderm induction.
Mol Cells 1999 Oct 31
PMID:Neuregulin induces the expression of mesodermal genes in the ectoderm of Xenopus laevis. 1059 38

The neuropeptide calcitonin gene-related peptide (CGRP) expressed by one-third of rat dorsal root ganglion (DRG) neurons mediates pain sensation and vasodilation. The developmental regulation of CGRP is poorly understood, but may involve target-derived factors from skin or viscera. Few embryonic DRG neurons in defined culture express CGRP, indicating inductive signals are required. Follistatin blocked CGRP expression induced by serum or skin-conditioned medium, implicating transforming growth factor beta (TGFbeta) family members. Activin or bone morphogenetic proteins (BMPs) 2, 4, or 6 stimulated CGRP expression in 60% of DRG neurons. Brief BMP4 application supported maximal CGRP induction, suggesting that BMP4 is a "switch" rather than a continuous modulator of neuropeptide phenotype. DRG expressed corresponding receptor subunits and exhibited Smad1 transcription factor nuclear translocation following BMP stimulation. BMP mRNAs were present in embryonic targets innervated by CGRP-expressing neurons. Thus, specific TGFbeta family members are candidate regulators of CGRP expression in sensory neurons.
Mol Cell Neurosci 1999 Dec
PMID:Activin and bone morphogenetic proteins induce calcitonin gene-related peptide in embryonic sensory neurons in vitro. 1065 56


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