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

---

Query: EC:2.7.11.1 (protein kinase)
81,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of FSH on goat follicular development, granulosa cell apoptosis and steroidogenesis and its mediation by insulin-like growth factor (IGF)-I were studied through both in vivo and in vitro experiments. The FSH treatment was begun on Day 9 after estrus and consisted of injections twice a day for 3 days in decreasing doses (7.5-7.5-5.0-5.0-2.5-2.5 mg). Does in both treatment and control groups were slaughtered for ovaries on Day 12. Granulosa cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). Expression of IGF-I and IGF-II mRNA was determined by RT-PCR, while concentrations of progesterone (P4), estradiol (E2), IGF-I and IGF-II were measured by radioimmunoassay (RIA). Following parameters increased significantly (P<0.05) after the FSH treatment: follicle number (5.0+/-1.5 versus 9.0+/-2.0 per ovary), the level of E2 (0.1+/-0.1 ng/ml versus 0.7+/-0.2 ng/ml), the E2/P4 ratio (0.7+/-0.4 versus 4.7+/-3.0) and the concentrations of IGF-I (0.5+/-0.2 ng/ml versus 119.4+/-15.1 ng/ml) and IGF-II (0.12+/-0.03 ng/ml versus 40.9+/-18.7 ng/ml) in follicular fluid of the medium sized (3-5 mm) follicles and in the ovarian cortex the relative quantity of IGF-I mRNA (0.37+/-0.17 versus 0.90+/-0.12 Max OD). In contrast, the ratio of apoptotic granulosa cells in these follicles was reduced significantly (0.53+/-0.1 versus 0.10+/-0.01, P<0.05). In large (>5 mm) follicles, however, only the follicle number (2.3+/-0.7 versus 7.0+/-1.5 per ovary) and the level of IGF-I (38.4+/-11.0 ng/ml versus 87.3+/-13.9 ng/ml) increased significantly (P<0.05), whereas other values did not change. In vitro culture of granulosa cells showed that FSH significantly (P<0.05) enhanced IGF-I production (12.7+/-2.1 ng/ml versus 26.+/-21.9 ng/ml) by these cells, and both FSH and IGF-I reduced the ratios of apoptotic cells (from 0.7+/-0.07 to 0.3+/-0.1 and 0.2+/-0.04, respectively) and the effect was additive when both were used together. H89, the PKA pathway inhibitor, blocked the effect of FSH on granulosa cell apoptosis and IGF-I production in vitro. These results indicated that FSH mainly enhanced the development of medium sized follicles in the goat by suppressing the apoptosis of granulosa cells via increasing production of IGF-I and steroids, possibly through the PKA pathway.
...
PMID:The effect of follicle-stimulating hormone on follicular development, granulosa cell apoptosis and steroidogenesis and its mediation by insulin-like growth factor-I in the goat ovary. 1458 Jun 51

Ser/Thr phosphorylation of insulin receptor substrate IRS-1 regulates insulin signaling, but the relevant phosphorylated residues and their potential functions during insulin-stimulated signal transduction are difficult to resolve. We used a sequence-specific polyclonal antibody directed against phosphorylated Ser(302) to study IRS-1-mediated signaling during insulin and insulin-like growth factor IGF-I stimulation. Insulin or IGF-I stimulated phosphorylation of Ser(302) in various cell backgrounds and in murine muscle. Wortmannin or rapamycin inhibited Ser(302) phosphorylation, and amino acids or glucose stimulated Ser(302) phosphorylation, suggesting a role for the mTOR cascade. The Ser(302) kinase associates with IRS-1 during immunoprecipitation, but its identity is unknown. The NH(2)-terminal c-Jun kinase did not phosphorylate Ser(302). Replacing Ser(302) with alanine significantly reduced insulin-stimulated tyrosine phosphorylation of IRS-1 and p85 binding and reduced insulin-stimulated phosphorylation of p70(S6K), ribosomal S6 protein, and 4E-BP1; however, this mutation had no effect on insulin-stimulated Akt or glycogen synthase kinase 3beta phosphorylation. Replacing Ser(302) with alanine reduced insulin/IGF-I-stimulated DNA synthesis. We conclude that Ser(302) phosphorylation integrates nutrient availability with insulin/IGF-I signaling to promote mitogenesis and cell growth.
...
PMID:Nutrient-dependent and insulin-stimulated phosphorylation of insulin receptor substrate-1 on serine 302 correlates with increased insulin signaling. 1462 99

Grb10 is a member of a superfamily of adaptor proteins that includes Grb7 and Grb14. This family of proteins shares a common overall structure, including an N-terminal region harboring a conserved proline-rich motif, a central Pleckstrin homology (PH) domain, a C-terminal Src homology 2 (SH2) domain, and a conserved region located between the PH and the SH2 domains (BPS). Grb10 directly interacts with a number of mitogenic receptor tyrosine kinases including the insulin (IR) and insulin-like growth factor-I (IGF-IR) receptor. Grb10 binds to the regulatory kinase loop of the insulin receptor (IR) via its SH2 and BPS domains. In addition to receptor tyrosine kinases, Grb10 has also been found to interact with non-receptor tyrosine kinases such as Tec and Bcr-Abl, and other cellular signaling molecules such as Raf-1 and the mitogen activated protein (MAP) kinase kinase, MEK. Overexpression of Grb10 has been shown to inhibit or stimulate insulin/IGF-I signaling depending on the expression levels of the specific isoforms, specific cell context, and/or physiologic endpoint. Genetic imprinting of Grb10 has been linked to the congenital disease, Silver-Russell syndrome, which is characterized by pre- and post-natal growth deficiency. This data suggests that Grb10 may function during embryogenesis in regulating insulin/IGF-I signaling as these growth factors play important roles during development. A role of Grb10 as a potent growth inhibitor during was implicated when disruption of the mGrb10 gene in mice resulted in overgrowth of mutant embryos and neonates. Grb10 is expressed in the central nervous system of mice and rats, which suggests that this protein may regulate neuronal insulin signaling and energy metabolism, consistent with its reported role in metabolic insulin action in fat and muscle cells. An important area of future investigation will be to elucidate the mechanism underlying Grb10's ability to regulate peptide hormone action including insulin/IGF-I signaling and to study the physiological role of this adaptor protein in cellular and animal models.
...
PMID:Grb10: more than a simple adaptor protein. 1476 76

A critical question in developmental neurobiology is how stem and progenitor cells interpret multiple signals to decide whether to proliferate or exit the cell cycle. Insulin-like growth factor (IGF)-I and fibroblast growth factor (FGF)-2 have known functions individually in development of neural stem cells as well as more restricted neuronal and glial progenitor cells. The goal of this study was to elucidate how IGF-I and FGF-2 coordinately regulate the cell cycle machinery in primary oligodendrocyte progenitors (OPs). IGF-I/FGF-2 synergistically increased the numbers of OP cells recruited into S phase. IGF-I enhanced FGF-2 induction of cyclin D1, activation of G(1) cyclin-cyclin-dependent kinase (cdk) complexes, and hyperphosphorylation of retinoblastoma protein (pRb). Moreover, IGF-I was required for G(2)/M progression. In contrast, FGF-2 decreased levels of the cdk inhibitor p27(Kip1) associated with cyclin E-cdk2. These studies provide a mechanistic basis for coordinate regulation of cell cycle progression in progenitor cells by multiple growth factors.
...
PMID:IGF-I and FGF-2 coordinately enhance cyclin D1 and cyclin E-cdk2 association and activity to promote G1 progression in oligodendrocyte progenitor cells. 1503 76

A common alternative therapy for benign prostatic hyperplasia (BPH) is the extract from the fruit of saw palmetto (SPE). BPH is caused by nonmalignant growth of epithelial and stromal elements of the prostate. IGF action is important for prostate growth and development, and changes in the IGF system have been documented in BPH tissues. The main signaling pathways activated by the binding of IGF-I to the IGF-I receptor (IGF-IR) are the ERK arm of the MAPK cascade and the phosphoinositol-3-kinase (PI3K)/protein kinase B (PKB/Akt) cascade. We tested the hypothesis that SPE suppresses growth and induces apoptosis in the P69 prostate epithelial cell line by inhibiting IGF-I signaling. Treatment with 150 microg/ml SPE for 24 h decreased IGF-I-induced proliferation of P69 cells and induced cleavage of the enzyme poly(ADP-ribose)polymerase (PARP), an index of apoptosis. Treatment of serum-starved P69 cells with 150 microg/ml SPE for 6 h reduced IGF-I-induced phosphorylation of Akt (assessed by Western blot) and Akt activity (assessed by an Akt kinase assay). Western blot analysis showed that SPE reduced IGF-I-induced phosphorylation of the adapter protein insulin receptor substrate-1 and decreased downstream effects of Akt activation, including increased cyclin D1 levels and phosphorylation of glycogen synthase kinase-3 and p70(s6k). There was no effect on IGF-I-induced phosphorylation of MAPK, IGF-IR, or Shc. Treatment of starved cells with SPE alone induced phosphorylation the proapoptotic protein JNK. SPE treatment may relieve symptoms of BPH, in part, by inhibiting specific components of the IGF-I signaling pathway and inducing JNK activation, thus mediating antiproliferative and proapoptotic effects on prostate epithelia.
...
PMID:Saw palmetto extract suppresses insulin-like growth factor-I signaling and induces stress-activated protein kinase/c-Jun N-terminal kinase phosphorylation in human prostate epithelial cells. 1503 18

We previously demonstrated that FSH alone or in combination with IGF-I activated the porcine steroidogenic acute regulatory protein gene promoter in a concerted manner in primary cultures of granulosa cells. Studies were undertaken to further delineate cis- and trans-acting elements of the porcine promoter and mechanisms mediating FSH stimulation and its augmentation by IGF-I. Mutation of several putative regulatory elements localized hormone-stimulated activity to the highly conserved GATA site and identified novel nucleotides downstream as a functional CCAAT/enhancer binding protein (C/EBP)beta site. In granulosa cell nuclear extracts, GATA-4 and C/EBPbeta formed a high-molecular-weight complex with an oligonucleotide spanning -76 to -32 bp of the porcine promoter. The intensity of this high-molecular-weight complex was increased in granulosa cell nuclear extracts by treatment with FSH alone and was enhanced with the combination of FSH and IGF-I at 2-3 h of treatment. GATA-4 and C/EBPbeta proteins were uniformly expressed with all treatments at time points associated with increased DNA binding. Treatment (2 h) with FSH alone or FSH + IGF-I increased phosphorylation of GATA-4 on a protein kinase A consensus site. The 38-kDa isoform of C/EBPbeta exhibited greater phosphorylation with FSH + IGF-I treatment. Porcine luteal cell nuclear extracts also demonstrated GATA-4 and C/EBPbeta binding to the -76 to -32 bp region of the promoter providing evidence for their cooperation in vivo. These data indicate that GATA-4 and C/EBPbeta are both required for FSH +/- IGF-I stimulation of the porcine steroidogenic acute regulatory protein gene promoter in homologous granulosa cell cultures.
...
PMID:Concerted regulation of the porcine steroidogenic acute regulatory protein gene promoter activity by follicle-stimulating hormone and insulin-like growth factor I in granulosa cells involves GATA-4 and CCAAT/enhancer binding protein beta. 1505 51

Ionizing or ultraviolet radiation-induced cellular survival signaling pathways induce development of cancer and insensitivity of tumor cells to radiation therapy. Accumulating evidence suggests that the phosphatidylinositide 3-kinase (PI3K)/AKT signal pathway is a major contributor to radioresistance. In many cell types PI3K/AKT signaling is a key cytoprotective response downstream of the EGFR family receptors and mediated carcinogenesis. Cytokines, such as HGF, IGF-I, and IL-6 also protects cells against apoptosis induced by radiation through PI3K/AKT pathway. The mechanics by which PI3K/AKT signaling functions in radiation responses may include its regulation of mitochondrial proteins, transcription factors, translation machinery, and cell-cycle progression. In addition, cross-talk between the PI3K/AKT pathway and mitogen-activated protein kinases, protein kinase A, and protein kinase C signal pathway may also play an important role.
...
PMID:Phosphatidylinositide 3-kinase/AKT in radiation responses. 1516 54

Recent studies have demonstrated that H(2)O(2) acts as a second messenger of mitogenic signaling and that catalase is under the regulation of PKA and PKC signaling. Here we examined whether catalase binds any mitogenic signaling molecules. Our results indicated that serum stimulation of HeLa, Caco-2, and LiSa-2 cells, but not BJ-1 and primary human bronchial epithelial cells, resulted in catalase binding to Grb2. Whereas serum deprivation, butyrate, and herbimycin-A negatively regulated the binding, an extended culture of confluent Caco-2 cells resulted in binding of an additional but as yet unidentified molecule to the Grb2-catalase complex. Expression of active catalase nearly 15-fold over control level in Tet-off HeLa cells substantially increased binding to Grb2, and this was sensitive to 3-aminotriazole, a specific catalase inhibitor. Furthermore, fibrinogen, fibronectin, and laminin, but not collagen types I to V, hyaluronic acid, elastin, insulin, EGF, IGF-I, PDGF, or NGF, resulted in binding similar to that of serum. A mutation of tyrosine to phenylalanine at 447 abolished the binding capability of catalase to Grb2 in vitro. These results support the view that catalase (447)Tyr-Val-Asn-Val binds Grb2 upon phosphorylation in tumor cells when stimulated with serum or ligands for integrin receptors. This is the first report demonstrating that catalase binds a SH2 domain of the molecule and participates in integrin signaling.
...
PMID:Catalase binds Grb2 in tumor cells when stimulated with serum or ligands for integrin receptors. 1518 56

cAMP has been found to play a role in mediating the negative regulation of cell motility, although its underlying molecular mechanism remains poorly understood. By using CHO (Chinese-hamster ovary) cells that express the EP2 subtype of PGE2 (prostaglandin E2) receptors, we provide evidence that an increase in cellular cAMP content leads to inhibition of cellular Rac activity, which serves as a mechanism for this negative regulation. In CHO cells expressing EP2, but not in vector control cells, PGE2 dose-dependently inhibited chemotaxis towards IGF-I (insulin-like growth factor-I), which is a Rac-dependent process, with the maximal 75% inhibition observed at 10(-8) M PGE2. EP2 stimulation failed to inhibit tyrosine phosphorylation either of IGF-I receptor or IRS-1 (insulin receptor substrate-1), or activation of phosphoinositide 3-kinase or Akt in response to IGF-I, but potently and dose-dependently inhibited IGF-I-induced activation of cellular Rac activity and membrane ruffling. However, PGE2 failed to inhibit Val12-Rac-induced membrane ruffling. Similar to the case of CHO cells, PGE2 inhibited PDGF (platelet-derived growth factor)-induced Rac activation and chemotaxis in vascular smooth muscle cells endogenously expressing EP2. The inhibitory effects of PGE2 on IGF-I-induced chemotaxis, membrane ruffling and Rac activation were faithfully reproduced by a low concentration of forskolin, which induced a comparable extent of cAMP elevation as with 10(-8) M PGE2, and were potentiated by isobutylmethylxanthine. The protein kinase A inhibitor Rp isomer of adenosine 3',5'-cyclic monophosphorothioate reduced PGE2 inhibition of Rac activation and chemotaxis. These results indicate that EP2 mediates Rac inhibition through a mechanism involving cAMP and protein kinase A, thereby inhibiting membrane ruffling and chemotaxis.
...
PMID:Inhibition of Rac activation as a mechanism for negative regulation of actin cytoskeletal reorganization and cell motility by cAMP. 1537 80

White adipose tissue plays a key role in the regulation of the energy balance of vertebrates. This tissue is also now recognized to secrete a variety of factors such as leptin, which is thought to be involved in the modulation of adipose mass. Unlike other tissues, adipose tissue mass has considerable capacity to expand. The review deals primarily on the regulation of development and metabolism of adipose tissue by growth hormone (GH) and the insulin-like growth factor (IGF) system, with a special focus on the pig. The anti-insulin effects of GH are well-documented in pigs as in other species. In vitro exposure of adipose precursor cells to GH leads to a decrease in differentiation of those cells in pigs, in contrast to data obtained in murine cell lines. In vivo treatment and prolonged in vitro incubation of adipose tissue or isolated adipocytes with GH result in a decrease in glucose transport and lipogenesis, especially at the level of the fatty acid synthase gene, resulting in a reduction of the lipid content and adipose tissue mass. The mechanism by which GH antagonizes insulin stimulation of lipogenesis is still unresolved, as it is not mediated by protein kinase A, protein kinase C and Janus kinase-2 at the signaling level, or upstream stimulatory factor 1 or sterol regulatory element binding protein-1 at the transcriptional level. GH is apparently the main regulator of IGF-I mRNA expression in adipose tissue, however, the effects of IGF-I on this tissue are rather unclear.
...
PMID:Regulation of development and metabolism of adipose tissue by growth hormone and the insulin-like growth factor system. 1545 Oct 72


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

---