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

Microsatellites and mitochondrial DNA sequences were studied for the two subspecies of orangutans (Pongo pygmaeus), which are located in Borneo (P. p. pygmaeus) and Sumatra (P. p. abelii), respectively. Both subspecies possess marked genetic diversity. Genetic subdivision was identified within the Sumatran orangutans. The genetic differentiation between the two subspecies is highly significant for ND5 region but not significant for 16s rRNA or microsatellite data by exact tests, although FST estimates are highly significant for these markers. Divergence time between the two subspecies is approximately 2.3 +/- 0.5 million years ago (MYA) estimated from our data, much earlier than the isolation of their geological distribution. Neither subspecies underwent a recent bottleneck, though the Sumatran subspecies might have experienced expansion approximately 82,000 years ago. The estimated effective population sizes for both subspecies are on the order of 104. Our results contribute additional information that may be interpreted in the context of orangutan conservation efforts.
J Mol Evol 2001 Jun
PMID:Genetic divergence of orangutan subspecies (Pongo pygmaeus). 1144 55

Activin signal transduction is regulated through multiple mechanisms. We have identified novel regulatory proteins that control activin functions either intracellularly or extracellularly. As intracellular molecules, PSD-95/Dlg/ZO-1 (PDZ) proteins that specifically associate with activin type II receptors (ActRIIs) were identified. We have named the molecules as activin receptor-interacting proteins (ARIPs). ARIP1 has two WW domains and five PDZ domains, associates not only with ActRIIs but also with Smads, and controls activin functions intracellularly in neuronal cells. Another ARIP we have found has only one PDZ domain, and is likely to be involved in intracellular trafficking and sorting of activin receptor complexes in the cell. As an extracellular regulatory protein, we have identified a novel follistatin-like protein, named follistatin-related gene (FLRG). Like follistatins, FLRG binds activins and bone morphogenetic proteins (BMPs) and controls their functions extracellularly. The mode of association of follistatin and FLRG with activins and their expression patterns are different, suggesting the distinct functions of follistatin and FLRG in vivo.
Mol Cell Endocrinol 2001 Jun 30
PMID:Intracellular and extracellular control of activin function by novel regulatory molecules. 1145 68

The identification and characterization of follistatin related protein (FSRP) suggests that the follistatin (FS) gene family may actually contain two sub-families. The first includes FS and FSRP by virtue of their high degree of structural homology and comparable activin-binding activity, while the second sub-family contains extracellular matrix proteins that possess one or more 10-cysteine FS domains, but do not bind activin or related TGF-beta family members. Characterization of FSRP indicates that it binds activin with similar affinity and selectivity as FS, but does not bind heparin. Furthermore, although FSRP inhibits activin-mediated gene transcription in heterologous assays, FSRP is much less active than FS in the rat pituitary bioassay. When overexpressed in transgenic mice, FSRP may lead to interruption of follicular development and fertility in females but appears to have only a modest effect on males. These results suggest that FSRP is a structural, but not necessarily a functional homologue of FS.
Mol Cell Endocrinol 2001 Jun 30
PMID:Follistatin-related protein (FSRP): a new member of the follistatin gene family. 1145 69

In this short review, the authors summarise the inhibin, activin and follistatin assays developed by the Oxford group and collaborators, and some of the main purposes for which they have been applied. Over 500 research publications have used these assays. We also discuss new assays recently developed at the request of our collaborators for particular applications, and comment on outstanding assay problems.
Mol Cell Endocrinol 2001 Jun 30
PMID:Enzyme immunoassays for inhibins, activins and follistatins. 1145 74

While the early studies of the inhibins, activins and follistatins concentrated on their role as endocrine regulators of FSH secretion, recent data has emphasized the local actions of the activins and follistatin. Inhibin, through its capacity to suppress FSH secretion can modulate numerous processes within the testis. However, to date, evidence to support a local role for inhibin is limited. In contrast, activin and its binding protein follistatin are produced by a large number of cell-types within the testis raising the possibility of a range of paracrine and autocrine actions. These include the modulation of androgen production, influence on the proliferation of Sertoli cells and germ cells as well as the capacity to influence the structural and functional features of mitochondria within germ cells. Some of these actions are carefully controlled in a temporal relationship during the development of testicular function in the rat in which there is no separation in time between birth and the onset of spermatogenesis. Given the range of actions of activin in different cell-types, recognition of systems that are designed to modulate its actions are crucial in enhancing our understanding of how these many roles can be compartmentalized.
Mol Cell Endocrinol 2001 Jun 30
PMID:Inhibins, activins and follistatin: actions on the testis. 1145 76

Unexplained fetal death in utero in late pregnancy represents an increasing proportion of perinatal deaths. It has been assumed that critical hypoxia is the likely mechanism underlying these losses, but the lack of a physiological marker has hampered both confirmation and prediction which could lead to timely intervention. In this paper, we report studies on hypoxia that we have performed in chronically cannulated late pregnant sheep, complemented by parallel investigations undertaken in human pregnancies. Our initial studies were directed towards determining activin secretion in the fetus and mother during late gestation, and immediately after fetal surgery using a sheep model. This led us to propose that there may be a relationship between hypoxia and activin A, follistatin and prostaglandin (PG) release from the feto-placental unit. Subsequent studies have been directed towards examining this potential relationship in sheep and in humans with compromised pregnancies. As a result of these studies, we have identified a potential mechanism by which activin A may be involved in regulating the response of the fetus to hypoxic insult. Activin A and follistatin concentrations increased in late gestation in ovine maternal plasma and in fetal fluids. Feto-placental hypoxemia or maternal isocapnic hypoxemia, leading to fetal hypoxia, were specific triggers for an acute increase in fetal activin A and follistatin concentrations during late gestation. The source and secretion of activin A, follistatin, and the associated release of PGE(2,) from within the feto-placental unit varied according to the site of the insult. The concomitant secretion of activin A and PGE(2) into the fetal circulation and amniotic fluid during reduced uterine blood flow provides an insight into the physiological regulatory mechanisms that might be involved. Changes observed in maternal activin A concentrations in mid and late gestation in the human may also be associated with fetal compromise. In human pregnancies, elevated activin A concentrations were observed in maternal plasma in mid and late gestation, in association with severe pre-eclampsia and with severe fetal growth restriction, compared to those observed in pregnancies with constitutionally small, healthy fetuses. Activin A was also elevated in maternal and arterial cord plasma in women at term during labour and immediately prior to undergoing emergency Caesarean section for failure to progress. These findings offer exciting new possibilities to gain insights into the mechanisms that underlie the maintenance of fetal wellbeing and provide a rationale for the potential that activin A may prove to be a useful clinical marker of fetal distress.
Mol Cell Endocrinol 2001 Jun 30
PMID:Physiological and regulatory roles of activin A in late pregnancy. 1145 82

The normal human prostate expresses inhibin and activin subunits. In prostate cancer, the inhibin alpha subunit gene is down regulated and this is associated with loss of heterozygosity (LOH) at the gene locus and methylation of the promoter. These data support the hypothesis that the inhibin alpha subunit is tumor suppressive in the prostate. The pluripotent effects of activins and the similarities to transforming growth factor beta (TFGbeta) suggest a role for activins in progression to malignancy, whereby, the normal growth inhibitory action of activin A observed on benign cells is lost with the acquisition of activin resistance in prostate cancer cells. The mechanisms of rendering tumor cells resistant to activin A may include: alteration in activin binding protein (follistatin) synthesis and/or dimerisation with activin beta(C) to form novel activin dimers. The contribution of the activin signalling cascade to malignancy requires further evaluation to identify the synergies and differences to other members of the TGFbeta superfamily.
Mol Cell Endocrinol 2001 Jun 30
PMID:The contribution of inhibins and activins to malignant prostate disease. 1145 85

The inflammatory cascade is a multifactorial process regulated by interwoven cytokine and growth factor networks. This review summarizes the emerging evidence that implicate activin A and follistatin in inflammatory processes. Our recent studies have determined that activin A is released early in the cascade of circulatory cytokines during systemic inflammatory episodes, roughly coincident with tumour necrosis factor (TNF)-alpha and before interleukin (IL)-6 and follistatin. The source(s) of this activin A are not yet established, but prime candidates are monocytes/macrophages, other immune cell types or vascular endothelial cells. Clinical data are limited, but activin beta(A) subunit mRNA or activin A protein is elevated in inflammatory bowel diseases and inflammatory arthropathies, and circulating concentrations of follistatin are elevated in patients with sepsis. In more mechanistic approaches, in vitro studies show that activin A can have both pro- and anti-inflammatory actions on key inflammatory mediators such as TNFalpha, IL-1beta and IL-6. Furthermore, there is emerging understanding of how the intracellular signaling pathway for activin A, incorporating Smads, may interact with and be modulated by other key regulatory cytokines and growth factors.
Mol Cell Endocrinol 2001 Jun 30
PMID:Evidence for activin A and follistatin involvement in the systemic inflammatory response. 1145 86

Activin A inhibits branching tubulogenesis of the kidney during development. Activin A also inhibits branching tubulogenesis in MDCK cells, an in vitro tubulogenesis model. On the other hand, follistatin, an antagonist of activin A, reverses the effect of activin A and induces branching tubulogenesis. Follistatin also promotes tubular regeneration after ischemia/reperfusion injury. The activin/follistatin system is one of the important regulatory systems modulating developmental and regeneration processes of the kidney.
Mol Cell Endocrinol 2001 Jun 30
PMID:Role of the activin-follistatin system in the morphogenesis and regeneration of the renal tubules. 1145 89

The mRNA expression patterns of activin beta(A) and follistatin in the uterus and embryo, the mRNA expression of the activin receptor II in the embryo, and the localization in the uterus of the immunoreactive activin beta(A) and the receptor II proteins in the uterus were examined at gestation days 7-12 after ovulation in pig. Activin was located predominantly at the mesometrial side of the uterus during all stages of pregnancy studied. Follistatin mRNA was absent in the uterus during these stages, suggesting that activin of uterine origin is not inhibited by intra-uterine follistatin. The receptor was localized throughout the glandular and luminal epithelium of the uterus. In the embryo, activin was expressed predominantly in the epiblast before unfolding, but after unfolding of the epiblast activin expression shifted to the trophoblast. The expression pattern of follistatin mRNA was contrarily to that of activin, i.e., before unfolding predominantly in the trophoblast (days 8-9), and shifted to the epiblast at day 10. During streak stages, follistatin was detected in the node and primitive streak. Activin receptor II mRNA was first detected at day 8 in the embryoblast. At day 11, it was expressed in trophoblast cells near the epiblast, and in the first ingressing mesoderm cells. During the streak stages, it was expressed predominantly in the trophoblast. The presence of activin and its receptor in uterine epithelium and early embryonic tissues indicate that both embryonic and uterine activin are involved in intra-uterine processes, such as attachment and early embryonic development. Mol. Reprod. Dev. 59: 390-399, 2001.
Mol Reprod Dev 2001 Aug
PMID:Uterine-embryonic interaction in pig: activin, follistatin, and activin receptor II in uterus and embryo during early gestation. 1146 75


<< Previous 1 2 3 4 5 6 7 8 9 10