Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.10.2 (focal adhesion kinase)
44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An enzyme immunoassay (EIA) test (Ortho Diagnostic Systems Ltd) was evaluated against cell culture for the detection of chlamydial genital infection. Specimens were obtained from 409 patients (204 men and 205 women). Sensitivity, specificity, predictive value of a positive result (PVP) and predictive value of a negative result (PVN) for the new test compared to cell culture were respectively 73.1%, 93.8%, 63.3% and 96% for men and 80%, 95.6%, 71.4% and 97.2% for women. Discrepancies were further evaluated by repeating the EIA, and by direct immunofluorescence (IF) on the EIA transport buffer. The sensitivity, specificity, PVP and PVN of the EIA against the combination of cell culture and direct IF were respectively 76.7%, 96%, 76.7% and 96% for men, and unchanged for women. Overall agreement between the EIA and the combination of cell culture and direct IF was 93.4%. The EIA is rapid and simple to perform and does not require elaborate equipment.
Int J STD AIDS 1990 May
PMID:Comparison of an enzyme immunoassay (Ortho) with cell culture and immunofluorescence for the detection of genital chlamydial infection. 208 92

Ovariectomized, adult female rats, with or without estradiol replacement, were kindled by daily amygdala stimulation. Kindling acquisition varied with the intra-amygdala site of stimulation. During stimulation of the medial (AME) or central (ACE) nucleus, the only effect of estradiol replacement (E), compared to non-replaced rats (nE), was to significantly decrease the number of trials with afterdischarge (AD) during early kindling (stage 0). In rats receiving stimulation of the cortical nucleus (ACO) or the baso-lateral group of nuclei (ABL), a similar effect of estradiol was extended through stage 1. In addition, nE rats with ACO or ABL electrodes required significantly more trials with AD and accumulated more than twice the sec of AD during the late stages of kindling, compared to E rats and regressed to lower stage responses between the first stage 4 and last stage 5 responses; regressed responses never occurred in E rats. Estradiol also significantly decreased the prekindling AD threshold of the AME and ACE. These results indicate that estradiol accelerates early stage kindling, likely by proconvulsive properties to increase excitability within immediate amygdala projections. During late kindling stages, estradiol may participate in reinforcing or sustaining the convulsive readiness of kindling circuits established during bilateral recruitment. The site of action for this latter effect of estradiol may reside within circuits accessed by stimulation of the ACO or ABL, and not the AME or ACE.
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PMID:Acquisition of amygdala-kindled seizures in female rats: relationship between the effect of estradiol and intra-amygdaloid electrode location. 368 62

MCF-7 human breast carcinoma cultures grown in the presence of 17-beta estradiol form solid, multicellular nodules, a process that reflects changes in cell-substrate adhesions and loss of growth inhibition. We examined the effects of estradiol on the status of tyrosine phosphorylation in focal adhesion kinase (FAK) and the association of FAK with paxillin using immunoprecipitations and then probing western blots for FAK, phosphotyrosine, and paxillin. Culture of MCF-7 cells for seven days in the presence of 1 nM E2 resulted in decreased tyrosine phosphorylation of FAK compared to controls. The estradiol-induced effect was blocked by 100 nM of the estrogen receptor antagonist 4-hydroxytamoxifen, indicating dephosphorylation of FAK is an estrogen receptor-mediated event. FAK immunoprecipitated from either estradiol or DMSO-treated cells phosphorylated the exogenous substrate poly(Glu,Tyr), suggesting that the potential kinase activity of FAK was not changed by estradiol. Estradiol treatment also resulted in a reduced association between FAK and paxillin. The decreased phosphorylation levels and reduced association between FAK and paxillin may be important steps leading to the loss of stable focal contacts and loss of growth inhibition during MCF-7 nodulation.
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PMID:Decreased tyrosine phosphorylation of focal adhesion kinase after estradiol treatment of MCF-7 human breast carcinoma cells. 987 83

The cytokine interleukin 6 (IL-6), a major mediator of immune and acute phase responses of the liver, has been implicated in the termination of pregnancy once expressed in the uterus. This study was undertaken to investigate the expression and regulation of genes encoding IL-6 and IL-6 receptor (IL-6R) in rat decidual tissue. Total RNA obtained from rat decidual tissue on different days of pseudopregnancy was analyzed by RT-PCR using specific primers for IL-6, IL-6R, and 130-kDa glycoprotein (gp130). Ribosomal L19 primers served as an internal control. IL-6R and gp130 were found to be expressed in the decidua throughout development, while no messenger RNA (mRNA) for IL-6 was detected. Interestingly, within several hours of culture, decidual explants acquired the ability to express IL-6. The apparent ability of decidual cells to express IL-6 and its lack of expression in vivo led us to examine whether the IL-6 gene is actively inhibited. Primary decidual cells were cultured in the presence of estradiol, progesterone, or PRL. Progesterone showed no effect, whereas estradiol and PRL reduced the level of IL-6 mRNA expression. To examine the mechanism by which these hormones inhibit IL-6 expression, we used a simian virus 40-transformed decidual cell line (GG-AD), which expresses only estrogen receptor-beta (ERbeta). Like primary decidual cells in culture, GG-AD cells express IL-6, IL-6R, and gp130 mRNA. When cultured in the presence of estradiol (0-100 ng/ml), mRNA for IL-6 and its receptor components were down-regulated in a dose-dependent manner. Estradiol also caused a dose-dependent decrease in IL-6 protein secretion into the culture medium. The inhibitory effect of estradiol on IL-6 mRNA expression was reversed by the antiestrogen ICI-164,384. Similar inhibition of IL-6 and gp130 mRNA expression was observed with PRL treatment. However, PRL had no effect on IL-6R mRNA levels. PRL inhibition of IL-6 expression was totally reversed by tyrphostin AG490, a JAK2 inhibitor. In summary, the results of this investigation indicate that IL-6 expression, which is detrimental to the maintenance of pregnancy, is inhibited in the rat decidual tissue. This inhibition is induced by PRL and estradiol, which down-regulate not only IL-6 expression, but also the expression of IL-6 receptor and signaling proteins. The results also suggest that PRL signaling to the IL-6 gene is mediated through the long form of PRL receptor and involves JAK2 activation, whereas that of estradiol can be transduced by estrogen receptor-beta.
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PMID:The expression of interleukin-6 (IL-6), IL-6 receptor, and gp130-kilodalton glycoprotein in the rat decidua and a decidual cell line: regulation by 17beta-estradiol and prolactin. 1049 97

Estradiol and insulin-like growth factor-I (IGF-I) interact in the hypothalamus to regulate neuronal function, synaptic plasticity and neuroendocrine events. However, the molecular mechanisms involved in these interactions are still unknown. In the present study, the effect of estradiol on the signaling pathways of IGF-I receptor has been assessed in the hypothalamus of young adult ovariectomized rats, using specific antibodies for the phosphorylated forms of extracellular-signal regulated kinase (ERK) 1 and ERK2 and Akt/protein kinase B (Akt/PKB). Estradiol treatment resulted, between 6 and 24 h after systemic administration, in dose-dependent effects on the phosphorylation of ERK and Akt/PKB. Estradiol did not modify the level of ERK phosphorylation induced by intracerebroventricular administration of IGF-I. However, both hormones had a synergistic effect on the phosphorylation of Akt/PKB. These findings suggest that estrogen effects in the hypothalamus may be mediated in part by the activation of the signaling pathways of the IGF-I receptor.
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PMID:Synergistic interaction of estradiol and insulin-like growth factor-I in the activation of PI3K/Akt signaling in the adult rat hypothalamus. 1241 26

In the brain, as in other tissues, estradiol interacts with growth factors. One of the growth factors that is involved in the neural actions of estradiol is insulin-like growth factor-I (IGF-I). Estradiol and IGF-I cooperate in the central nervous system to regulate neuronal development, neural plasticity, neuroendocrine events and the response of neural tissue to injury. The precise molecular mechanisms involved in these interactions are still not well understood. In the central nervous system there is abundant co-expression of estrogen receptors (ERs) and IGF-I receptors (IGF-IRs) in the same cells. Furthermore, the expression of estrogen receptors and IGF-I receptors in the brain is cross-regulated. In addition, using specific antibodies for the phosphorylated forms of extracellular-signal regulated kinase (ERK) 1 and ERK2 and Akt/protein kinase B (Akt/PKB) it has been shown that estradiol affects IGF-I signaling pathways in the brain. Estradiol treatment results in a dose-dependent increase in the phosphorylation of ERK and Akt/PKB in the brain of adult ovariectomized rats. In addition, estradiol and IGF-I have a synergistic effects on the activation of Akt/PKB in the adult rat brain. These findings suggest that estrogen effects in the brain may be mediated in part by the activation of the signaling pathways of the IGF-I receptor.
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PMID:Interactions of estrogen and insulin-like growth factor-I in the brain: molecular mechanisms and functional implications. 1265 Jul 18

Estrogen receptor (ER)alpha and ERbeta are transcription factors that can be activated by both ligand binding and growth factor signaling. Estradiol increases ER activity in part by enhancing interactions between its carboxy-terminal, ligand-binding domain (LBD) and the p160/SRC (steroid receptor coactivator) and p300/CBP (cAMP response element binding protein (CREB) binding protein) families of coactivators. In the absence of ligand and the LBD, these cofactors can also interact with the amino-terminal (A/B) domain of ERs in vitro. SRC-1 also enhances the ligand-independent activity of the full-length receptor. Both ligand-independent and estradiol-induced ER activity are increased by phosphorylation at specific serine (Ser) residues in the A/B domain (Ser104/106 and Ser118 in ERalpha). In the case of ERbeta, phosphorylation enhances the ligand-independent recruitment and action of SRC-1. We show here that unliganded ERalpha can activate endogenous gene expression in MCF-7 cells, and that this activation is mediated in part by a p160 coactivator. In transfected HeLa cells, we show that the full-length ERalpha can interact physically and functionally with p160/SRCs and CBP in the absence of ligand and that mutation of Ser104/106/118 affects these interactions. Accordingly, ERalpha dephosphorylation decreases its ligand-independent interaction with SRC-1 and CBP in vitro. In HeLa cells, both Ser104/106 and Ser118 impinge on SRC-1 action by two mechanisms: 1) a seemingly indirect effect on SRC-1 recruitment that requires other receptor domains in addition to the A/B, consistent with our finding that the ligand-independent interaction between the A/B and the LBD and its enhancement by SRC-1 depend in part on Ser104/106/118; and 2) an effect on SRC-1 coactivation that can be observed in the absence of the LBD. Ser104/106/118 can also affect coactivation by a subset of coactivators in the presence of hormone, albeit to a lesser extent than in its absence. Altogether, our observations suggest that the enhancement of ERalpha activity by p160/SRCs and CBP can be regulated by phosphorylation and stress the importance of using full-length receptors to assess the role of the activation function-1 in cofactor recruitment.
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PMID:Ligand-independent interactions of p160/steroid receptor coactivators and CREB-binding protein (CBP) with estrogen receptor-alpha: regulation by phosphorylation sites in the A/B region depends on other receptor domains. 1271 2

Premenopausal women have a lower cardiovascular risk and a higher incidence of several autoimmune diseases involving blood vessels than men. Although the precise effects of estrogens on the cardiovascular system are largely unknown, recent data suggest that estrogens can exert direct regulatory effects on endothelial cells. In the present study, we show that 17beta-estradiol increases human umbilical vein endothelial cell attachment to the extracellular matrix proteins laminin-1, type IV collagen, type I collagen, and fibronectin. Estradiol enhanced adhesion most significantly to laminin-1 and to fibronectin-derived synthetic peptides containing an RGD sequence. Upon exposure to estradiol, an increase in beta1, alpha5 and alpha6 integrin mRNA was observed in subconfluent cells which was abrogated by treatment with cycloheximide. This increase was followed by a later enhancement in surface expression of the above integrins. In addition, integrin-mediated signaling was also enhanced by estrogens since an increase in tyrosine-phosphorylation of focal adhesion kinase induced by cell attachment was observed in estrogen-treated endothelial cells. Since integrins have an important role in mediating endothelial cell attachment, migration and differentiation, the increase in integrin expression and function induced by estradiol may be an important mechanism through which estrogens can promote neovascularization and vessel repair.
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PMID:Estradiol enhances endothelial cell interactions with extracellular matrix proteins via an increase in integrin expression and function. 1451 26

Estrogens can stimulate the proliferation of estrogen-responsive breast cancer cells by increasing their proliferative response to insulin-like growth factors. With a view to investigating the molecular mechanisms implicated, we studied the effect of estradiol on the expression of proteins implicated in the insulin-like growth factor signalling pathway. Estradiol dose- and time-dependently increased the expression of insulin receptor substrate-1 and the p85/p110 subunits of phosphatidylinositol 3-kinase but did not change those of ERK2 and Akt/PKB. ICI 182,780 did not inhibit estradiol-induced IRS-1 and p85 expression. Moreover, two distinct estradiol-BSA conjugate compounds were as effective as estradiol in inducing IRS-1 and p85/p110 expression indicating the possible implication of an estradiol membrane receptor. Comparative analysis of steroids-depleted and steroids-treated cells showed that IGF-I only stimulates cell growth in the latter condition. Nevertheless, expression of a constitutively active form of PI 3-kinase in steroid-depleted cells triggers proliferation. These results demonstrate that estradiol positively regulates essential proteins of the IGF signalling pathway and put in evidence that phosphatidylinositol 3-kinase plays a central role in the synergistic pro-proliferative action of estradiol and IGF-I.
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PMID:Estradiol regulates the insulin-like growth factor-I (IGF-I) signalling pathway: a crucial role of phosphatidylinositol 3-kinase (PI 3-kinase) in estrogens requirement for growth of MCF-7 human breast carcinoma cells. 1704 71

The importance of FOXO transcription factors in regulating different aspects of cellular homeostasis and apoptosis has become apparent. Akt/protein kinase B has been shown to phosphorylate and inactivate members of FOXO family of transcription factors. Akt and its upstream regulator, phosphatidylinositol-3 kinase (PI3K) are involved in rapid action of estrogen (E2) in different cells and tissues. The aim of the present study was to analyze the E2/PI3K/Akt/FOXO pathway in rat uterus. In response to E2, phosphorylation of Akt/PKB on Ser473 and FOXO1 on Ser256 and Thr24 residues increased but with distinct kinetics, regulating the activation and inactivation of Akt and FOXO1 proteins, respectively. The antiestrogen ICI 182,780 prevented E2 induced Akt activation suggesting that estrogen receptors mediate this effect of E2. Intrauterine injection of Wortmannin caused a decrease in the phosphorylation of Ser473 of Akt, and attenuated phosphorylation of its downstream target FOXO1 at Ser256 and at Thr24. However, the effect of E2 on phosphorylation of Thr24 showed a kinetic pattern distinct from that of Ser256. Our results suggest that the E2/PI3K/Akt/FOXO1 pathway in rat uterus is functioning even at the lack of ovarian hormones and responses to E2 treatment. Estradiol increases Akt phosphorylation through a Wortmannin sensitive way, presumably involving PI3K. The present work shows that PI3K plays a crucial role in the phosphorylation and inactivation of FOXO1 in vivo, indicating that the regulation of this transcription factor is a more complex event in uterine cells requiring further investigations.
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PMID:Effect of estrogen and inhibition of phosphatidylinositol-3 kinase on Akt and FOXO1 in rat uterus. 1743 23


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