• Glioblastoma (GBM), a very aggressive and incurable tumor, often results from constitutive activation of EGFR (epidermal growth factor receptor) and of phosphoinositide 3-kinase (PI3K). (sdbonline.org)
  • S6K1 (p70 ribosomal S6 kinase 1) is activated by insulin and growth factors via the PI3K (phosphoinositide 3-kinase) and mTOR (mammalian target of rapamycin) signalling pathways S6K1 regulates numerous processes. (dundee.ac.uk)
  • The PI-3K pathway regulates diverse neuronal activities, mainly through the downstream molecule Akt/protein kinase B. In addition to a critical role in neuronal survival12C15, PI3K/Akt signaling has been implicated in dendritic morphogenesis16, neuronal polarity and growth17, synaptogenesis and spinogenesis18, plasticity19, axon establishment, and axon elongation during development by phosphorylating glycogen synthase kinase (GSK)-3, which leads to GSK3 inactivation20C23. (estme.org)
  • Transformation by v-Src: Ras-MAPK and PI3K-mTOR mediate parallel pathways. (embl.de)
  • To address the possibility that activation of phosphatidylinositol-3-kinase (PI3K) and the mammalian target of rapamycin (mTOR/FRAP), represents one of these pathways, we have examined the effect of simultaneous inhibition of the Ras-MAPK and PI3K-mTOR pathways on transformation of CEF by v-Src. (embl.de)
  • Mutations in K-Ras and B-Raf activate the phosphoinositide 3-kinase (PI3K)/AKT and mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) signaling pathways. (biomedcentral.com)
  • Normally, upon the stimulations by growth factors (GFs), the receptor tyrosine kinases (RTKs) are activated, and then recruit PI3K protein complex on the membrane to generate phosphatidylinositol-3,4,5-triphosphate (PIP3) from phosphatidylinositol-4,5-biophosphate (PIP2) [ 2 ]. (biomedcentral.com)
  • Post-translational modifications (PTMs) are crucial for regulating PI3K/AKT signaling pathway, notably phosphorylation. (biomedcentral.com)
  • Tyrosine phosphorylation of RTKs, or adaptor proteins such as IRS-1 facilitate their binding with p85 regulatory subunits of PI3K, and then bring PI3K complex on membrane [ 2 ]. (biomedcentral.com)
  • cSH2 domain S690 phosphorylation decreases p85 binding affinity to tyrosine-phosphorylated proteins resulting in less PI3K membrane localization [ 15 ]. (biomedcentral.com)
  • To gain further knowledge about the PI3K-AKT-mTOR-S6K and the RAF-MEK-ERK-RSK signaling networks in myotubes, we analyzed changes in protein phosphorylation levels upon pathway activation and direct kinase inhibition on a global scale. (omicsdi.org)
  • To deepen our understanding of the PI3K-AKT-mTOR-S6K and the RAF-MEK-ERK-RSK signaling network in myotubes, we globally analyzed changes in protein phosphorylation levels upon kinase inhibition within these pathways. (omicsdi.org)
  • Receptor tyrosine kinases (RTKs) activate pathways mediated by serine-threonine kinases, such as the PI3K (phosphatidylinositol 3-kinase)-Akt pathway, the Ras-MAPK (mitogen-activated protein kinase)-RSK (ribosomal S6 kinase) pathway, and the mTOR (mammalian target of rapamycin)-p70 S6 pathway, that control important aspects of cell growth, proliferation, and survival. (omicsdi.org)
  • We identified a subset of proteins with RxRxxS/T sites for which phosphorylation was decreased by RTK inhibitors (RTKIs), as well as by inhibitors of the PI3K, mTOR, and MAPK pathways, and we determined the effects of small interfering RNA directed against these substrates on cell viability. (omicsdi.org)
  • Furthermore, EPO-induced neuroprotection as well as phosphorylation of the proapoptotic Bcl family member Bad was reduced by the phosphoinositide-3 kinase (PI3K) inhibitor LY294002. (jneurosci.org)
  • PI3K deactivates BAD via Akt-mediated phosphorylation and thus may inhibit hypoxia-induced apoptosis in neurons. (jneurosci.org)
  • The PTKc (catalytic domain) family to which this subfamily belongs, is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase (PI3K). (umbc.edu)
  • b) 4-Hydroxytamoxifen (but not tamoxifen), genistein (but not genistin), daidzein, and probably other nutritional and chemopreventive anti-cancer agents could up-regulate expression of p27 via receptor protein tyrosine kinases (RPTKs), phosphoinositide 3-kinase (PI3K), phosphoinosite-dependent kinase (PDK), Akt/PKB and mTOR. (biomedcentral.com)
  • Signaling through the phosphatidylinositol 3′-kinase (PI3K) pathway is crucial for metabolic responses to insulin, and defects in PI3K signaling have been demonstrated in type 2 diabetes. (diabetesjournals.org)
  • PTEN (MMAC1) is a lipid/protein phosphatase that can negatively regulate the PI3K pathway by dephosphorylating phosphatidylinositol (3,4,5)-triphosphate, but it is unclear whether PTEN is physiologically relevant to insulin signaling in vivo. (diabetesjournals.org)
  • Phosphatidylinositol 3′-kinase (PI3K) is a crucial signaling enzyme whose activity is regulated by a variety of biological stimuli, including insulin ( 1 ). (diabetesjournals.org)
  • Activated PI3K phosphorylates the 3′-position of the ring in inositol phospholipids, generating phosphatidylinositol ( 3 , 4 ), diphosphate, and phosphatidylinositol (3,4,5)-triphosphate (PIP3). (diabetesjournals.org)
  • The lipid products of PI3K initiate phosphorylation and activation of Akt, which is believed to act as a downstream mediator of many of the metabolic effects of insulin ( 5 , 6 ). (diabetesjournals.org)
  • Thus, the expression of inactive PI3K mutants or chemical agents, such as wortmannin and LY294002 that interfere with PI3K activity, inhibit Akt phosphorylation, glucose uptake, and glycogen and lipid synthesis in vitro ( 7 , 8 ). (diabetesjournals.org)
  • PTEN also has phosphoinositide 3′-phosphatase activity and is therefore capable of suppressing PI3K signaling by dephosphorylating PIP3 ( 11 , 12 ). (diabetesjournals.org)
  • Function of RSV has been extensively explored for its powerful antioxidant capacity and specific effects on proteins and/or signaling cascades, such as Sirt1, adenosine monophosphate activated kinase, phosphatidylinositol-3 kinase (PI3K)/Akt, and JNK/nuclear factor-kappa B (NF- B) in DN both in vivo and in vitro [ 8 - 10 ]. (hindawi.com)
  • found that RSV decreased the activity of PI3K/Akt phosphorylation, resulting in a decrease in BCL-2-associated X protein (BAX) and increases in BCL-2 and superoxide dismutase production in diabetic kidney [ 8 ]. (hindawi.com)
  • Activated TPKR could activate its downstream signaling elements, like Ras/Raf/MEK/ERK, PI3K/Akt/eIF4E, PI3K/Akt/eNOS and PLC-gamma/PKC pathways. (biomedcentral.com)
  • The protein kinase C inhibitor bis(indolyl)maleimide inhibitor BIM1 is clearly seen in the structure of PKCiota (residue 574-turn motif), need to be phosphorylated towards a PKCbeta-specific inhibitor site-directed mutagenesis of the compound for its full activation and co-crystallized as an asymmetric pair which is mediated by 3-phosphoinositide-dependent protein kinase-1 (PDK1) are downstream characteristics of PKCs and PKB/AKT. (wikipedia.org)
  • The bound BIM1 inhibitor blocks the ATP-binding site and puts the kinase domain into an intermediate open conformation. (wikipedia.org)
  • The value of such calculations lies in understanding a variant was designed which showed improved binding characteristics of configurationally stable atropisomeric bisindolylmaleimides where the two kinase domains, and two different inhibitor conformers bind in different orientations, the hinge region of staurosporine-Pim-1 resembles co-crystallized as an asymmetric pair of biosynthetically 'related' indolocarbazole analogs. (wikipedia.org)
  • The protein kinase C inhibitor bisindolyl maleimide 2 binds with reversed orientations to different conformations of protein kinase A". J Biol Chem. (wikipedia.org)
  • Both the PI-3K inhibitor wortmannin and PKC inhibitor calphostin C blocked the phosphorylation of p70 S6K mediated by the growth factors. (nih.gov)
  • However, the mitogen-activated protein kinase (p42/44 MAPK) cascade inhibitor PD98059 had no effect on p70 S6K activation. (nih.gov)
  • Acanthamoeba -mediated brain endothelial cell death was abolished using LY294002, a phosphatidylinositol 3-kinase inhibitor. (asm.org)
  • PF-4708671 is the first S6K1-specific inhibitor to be reported and will be a useful tool for delineating S6K1-specific roles downstream of mTOR. (dundee.ac.uk)
  • Moreover, our recent study showed that Akt1 regulates the formation of NBI-74330 growth cones and functions through the phosphorylation of S14 on inhibitor of DNA binding 2 (Id2), which is a unfavorable regulator of basic helixCloopChelix transcription factors30. (estme.org)
  • Interestingly, while GT1b enhanced caspase-3 activity, DEVD, a caspase-3 inhibitor, failed to rescue DA neuronal death. (biomedcentral.com)
  • Moreover, a GSK-3β specific inhibitor, L803-mt, attenuated tau phosphorylation and rescued DA neurons from cell death in mesencephalic cultures. (biomedcentral.com)
  • Inhibition of the Ras-MAPK pathway by expression of the dominant-negative Ras mutant HRasN17 or by addition of the MAPK kinase (MEK) inhibitor PD98059 reduced several of these parameters but failed to block transformation. (embl.de)
  • The activity of this kinase is restricted to the G1-S phase, which is controlled by the regulatory subunits D-type cyclins and CDK inhibitor p16(INK4a). (thermofisher.com)
  • BI-D1870 is a specific inhibitor of the p90 RSK (ribosomal S6 kinase) isoforms in vitro and in vivo. (omicsdi.org)
  • Cultured neurons express EpoR, and the Janus kinase-2 (JAK-2) inhibitor AG490 abolished EPO-induced tolerance against OGD. (jneurosci.org)
  • The connection between p38 MAPK and NFκB-p65 was Selumetinib inhibited in concentration-dependent fashion by SB203580 a chemical inhibitor of p38 MAPK but not by SP600125 an inhibitor of JNK - another MAPK implicated in chemokine manifestation by HAdV-19 infected cells. (health-ground.com)
  • p27(Kip1) is a cyclin-dependent kinase inhibitor. (biomedcentral.com)
  • Up-regulation of the expression of p27 is likely due to the activation of translation rather than transcription of p27 because (a) up-regulation is mediated by the 5'-untranslated region (-575) of the p27 gene and (b) the antibiotic actinomycin D, an inhibitor of transcription, did not attenuate the up-regulation of p27. (biomedcentral.com)
  • The cyclin-dependent kinase (CDK) inhibitor p27(Kip1) is a key cell-cycle regulator of G1-to-S phase transition [ 1 ]. (biomedcentral.com)
  • Where Thr-412 (activation loop of the kinase domain) at PKCiota/lambda phosphorylates glyceraldehyde-3-phosphate dehydrogenase (GAPDH) that sort cargo to the anterograde pathway the phosphorylation pathway(s) involved in this phenomenon mimic glutamate and can adopt two limiting diastereomeric (syn and anti) conformation biosynthetically related indolocarbazole analogs and in Proto-oncogene serine/threonine-protein kinase Pim-1-Peptide as a phosphorylation target including itself. (wikipedia.org)
  • Our data provide novel evidence that a Akt/GSK-3β/tau-dependent, but not caspase-3 signaling pathway plays a pivotal role in GT1b-mediated neurotoxic actions on mesencephalic DA neurons. (biomedcentral.com)
  • However, the mitochondrial oxidative phosphorylation (OXPHOS) pathway in tumor cells has also been implicated in lung cancer metabolism. (spandidos-publications.com)
  • It has been reported that lung cancer cells exhibit upregulated expression of all key glycolytic enzymes [hexokinase 2 (HK2), phosphofructokinase and pyruvate kinase (PK)] ( 13 ), suggesting that the essential enzymes of the aerobic glycolytic pathway have a critical role in the development of lung carcinoma. (spandidos-publications.com)
  • The ↑[Ca 2+ ] i activates a signaling cascade that involves, sequentially, calcium-calmodulin, nitric oxide synthase, guanylyl cyclase, and protein kinase G. This signal transduction pathway enables Cl − to pass through vesicular channels and act as a counterion for the transport of H + , so that the vesicles of secretogogue-stimulated cells become acidic. (jneurosci.org)
  • Protein phosphorylation is crucial for signaling transduction of this pathway. (biomedcentral.com)
  • These ATG proteins also perform an important parallel role in 'noncanonical' autophagy, a lysosome-associated signaling pathway with key functions in immunity, inflammation, cancer, and neurodegeneration. (babraham.ac.uk)
  • Here, we identify a molecular pathway that links innate immunity to age-dependent l. (shengsci.com)
  • However, the host intracellular signaling pathways and the molecular mechanisms associated with Acanthamoeba -mediated HBMEC cytotoxicity have not been determined. (asm.org)
  • More specifically, substrates with certain FYVE domains (named after the first four proteins in this motif, Fab1, YotB, Vac1p, and EEA1) bind PIP, and these pathways have been implicated in vesicular trafficking or receptor-mediated endocytosis ( 5 ). (asm.org)
  • Thus, Akt may regulate growth cone dynamics through alternative signaling pathways including the phosphorylation of ERM proteins. (estme.org)
  • However, in recent years, there has been increasing evidence that metformin exerts its anticancer effects through the inhibition of oxidative phosphorylation (OXPHOS) of tumor cell mitochondria, and metabolic pathways based on metformin targeting have only recently become the focus of intensive research. (spandidos-publications.com)
  • Phospho-proteomics analysis and Western blots are used to demonstrate downstream signaling pathways of PIK3CA/p110α tyrosine phosphorylation. (biomedcentral.com)
  • PIK3CA/p110α phosphorylation at Y317 and Y508 play important role in tumorigenesis of colorectal cancer through two independent pathways. (biomedcentral.com)
  • The IRS proteins (IRS1-4) are the family of adaptors regulating metabolic and mitogenic signaling pathways ( Hanke and Mann , 2009 Hanke S and Mann M (2009) The phosphotyrosine interactome of the insulin receptor family and its substrates IRS-1 and IRS-2. (scielo.br)
  • Recent studies on the involvement of the G12 family of heterotrimeric G proteins (Gα12 and Gα13, the products of the GNA12 and GNA13 genes, respectively) in oncogenic pathways have uncovered a link between G12. (biomedcentral.com)
  • In addition, they play important roles in gene transcription (via activation of mitogen activated protein (MAP) kinase pathways and, in higher eukaryotes, the transcription factor NFκB), generation of reactive oxygen species, apoptosis, and cell-cycle progression. (biomedcentral.com)
  • We demonstrate that protein kinase N (PKN) facilitates mTORC1 signalling by repressing PI3KC2-β-mediated phosphatidylinositol-3,4-bisphosphate synthesis downstream of mTORC2. (nature.com)
  • Next, we observed that Acanthamoeba specifically activates phosphatidylinositol 3-kinase. (asm.org)
  • These results were further confirmed using brain microvascular endothelial cells expressing dominant negative forms of phosphatidylinositol 3-kinase. (asm.org)
  • This is the first demonstration that Acanthamoeba -mediated brain microvascular endothelial cell death is dependent on phosphatidylinositol 3-kinase. (asm.org)
  • Phosphatidylinositol 3-kinases (PI3Ks) are important signaling molecules that phosphorylate the 3′ OH position of the inositol ring of phosphoinositides (PIs), generating the second messengers PI(3)P, PI(3,4)P 2 , and PI(3,4,5)P 3 ( 4 , 17 ). (asm.org)
  • The recruitment of specific cytosolic proteins to intracellular membranes through binding phosphorylated derivatives of phosphatidylinositol (PtdIns) controls such processes as endocytosis, regulated exocytosis, cytoskeletal organization, and cell signaling. (embl.de)
  • We report here that Sac1p has a specific role in secretion and acts as an antagonist of the phosphatidylinositol 4-kinase Pik1p in Golgi trafficking. (embl.de)
  • Synthesis of new cyclitol compounds that influence the activity of phosphatidylinositol 4-kinase isoform, PI4K230. (embl.de)
  • The synthesis, chemical derivatization, and investigation of the inhibitory properties of novel cyclitol derivatives on the phosphatidylinositol 4-kinase enzymes PI4K55 and PI4K230 involved in the phosphatidylinositol cycle are reported. (embl.de)
  • PF cells were found to express regulatory (p85) and catalytic (p110α and p110β) subunits of phosphatidylinositol 3′-kinase (PI3′-kinase). (jneurosci.org)
  • Mechanistic target of rapamycin (mTOR) kinase functions in two multiprotein complexes: lysosomal mTOR complex 1 (mTORC1) and mTORC2 at the plasma membrane. (nature.com)
  • Activation of AMPK by low energy supply and phosphorylation of LKB1 results in an inhibition of mTOR , thus decreasing energy-consuming processes, in particular translation and, thus, cell growth. (sdbonline.org)
  • an effect that is dependent upon mTORC1 (mTOR complex 1). (dundee.ac.uk)
  • Akt-RSK-S6 kinase signaling networks activated by oncogenic receptor tyrosine kinases. (omicsdi.org)
  • For instance, Akt increased E3 ligase activity of Mdm2 by phosphorylation by preventing its autoubiquitination, thereby promotes UPS dependent degradation of p53, which is well known target of Mdm2. (estme.org)
  • The capability to temporally and spatially control these parts can be endowed by an evergrowing set of posttranslational adjustments which when covalently mounted on their substrates govern procedures including protein-protein relationships proteins localization and actions and proteins degradation (10). (healthweeks.com)
  • Using tobacco pollen tubes as a model, we addressed the signaling effects of PA by probing the functions of three most relevant enzymes that regulate the production and degradation of PA, namely, phospholipases D (PLD), diacylglycerol kinases (DGKs), and lipid phosphate phosphatases (LPPs). (frontiersin.org)
  • With the appropriate stimulus IκB kinase initiates phosphorylation and degradation of IκB therefore freeing NFκB to form transcriptionally active complexes that translocate to the nucleus [21-23]. (health-ground.com)
  • This apparent increase in p27 protein expression might have been due to either increased synthesis or decreased degradation, or a combination of both [ 1 ]. (biomedcentral.com)
  • The majority of inositol lipids reside in membranes and serve as substrates for kinases, phosphatases, and phospholipases. (asm.org)
  • which specifically inhibits the S6K1 isoform with a K-1 of 20 nM and IC50 of 160 nM PF-4708671 prevents the S6K1-mediated phosphorylation of S6 protein in response to IGF-1 (insulin-like growth factor 1), while having no effect upon the PMA-induced phosphorylation of substrates of the highly related RSK (p90 ribosomal S6 kinase) and MSK (mitogen- and stress-activated kinase) kinases. (dundee.ac.uk)
  • In contrast, BI-D1870 does not affect the agonist-triggered phosphorylation of substrates for six other AGC kinases. (omicsdi.org)
  • We developed a large-scale proteomic approach to identify more than 300 substrates of this kinase family in cancer cell lines driven by the c-Met, epidermal growth factor receptor (EGFR), or platelet-derived growth factor receptor alpha (PDGFRalpha) RTKs. (omicsdi.org)
  • PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. (umbc.edu)
  • Binding of insulin to its receptor activates the insulin receptor tyrosine kinase, resulting in autophosphorylation and phosphorylation of several substrates, including insulin receptor substrate (IRS)-1 through -4. (diabetesjournals.org)
  • Acute physiological elevation of IL-6 suppressed blood sugar metabolism and triggered insulin level of resistance by raising SOCS3 and via SOCS3-mediated inhibition of insulin receptor substrate (IRS)-1 and perhaps AMPK in center. (cancer-ecosystem.com)
  • PKC involvement can be accounted for by PKCγ and an isoform sensitive to inhibition by pseudoZ, probably PKCζ, which is activated via PI3′-kinase. (jneurosci.org)
  • Furthermore, EOPK suppressed PAK1 expression in a dose-dependent manner, and this suppression of PAK1 led to inhibition of ERK, AKT, and β-catenin activities. (biomedcentral.com)
  • A gene expression analysis revealed that deletion of Akt in liver led to the constitutive activation of Foxo1-dependent gene expression, but again, concomitant ablation of Foxo1 restored postprandial regulation, preventing the inhibition of the metabolic response to nutrient intake caused by deletion of Akt . (nature.com)
  • Inhibition of PTEN expression also dramatically reduced insulin concentrations in ob/ob mice, improved the performance of db/db mice during insulin tolerance tests, and increased Akt phosphorylation in liver in response to insulin. (diabetesjournals.org)
  • Sustained canonical Wnt signaling requires the inhibition of glycogen synthase kinase 3 (GSK3) activity by sequestration of GSK3 inside multivesicular endosomes (MVEs). (shengsci.com)
  • Immunoblot analysis revealed that GT1b inactivates Akt through dephosphorylation at both Ser473 and Thr308, subsequent dephosphorylation of GSK-3β, a substrate of Akt, and hyperphosphorylation of tau, downstream of GSK-3β. (biomedcentral.com)
  • Significantly the chromatin-associated RNF8 mediates substrate ubiquitylation at sites of DNA breaks which is vital for the ionizing rays (IR)-induced concentrate (IRIF) development of BRCA1 and 53BP1. (healthweeks.com)
  • Based on the phosphoproteomics data, we further examined target relationships of the basophilic kinases AKT, RSK and S6K, which share the substrate recognition motif RxRxxp[ST]. (omicsdi.org)
  • The phosphoproteomics data were used to define potential targets of the kinases AKT, RSK and S6K, which share the substrate recognition motif RxRxxp[ST]. (omicsdi.org)
  • It can be difficult to assess the individual functions of each AGC kinase because their substrate specificities are similar. (omicsdi.org)
  • Metz HE and Houghton AM (2011) Insulin receptor substrate regulation of phosphoinositide 3-kinase. (scielo.br)
  • In addition to binding to the insulin receptor, IRS1 also binds to and transmits signals from the receptors of prolactin, growth hormone (GH), leptin, vascular endothelial growth factor (VEGF), tropomyosin receptor kinase B (TrkB), anaplastic lymphoma kinase (ALK), insulin like growth factor (IGF1), and integrins ( Vuori and Ruoslathi , 1994 Vuori K and Ruoslahti E (1994) Association of insulin receptor substrate-1 with integrins. (scielo.br)
  • Phosphoinositides (PPIs) together with various kinases and phosphatases were described as specific lipids and enzymes with signaling functions earlier ( Martin, 1998 ). (frontiersin.org)
  • The insulin receptor exhibiting kinase activity is responsible for its autophosphorylation at the tyrosine residue site upon insulin binding. (encyclopedia.pub)
  • They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). (umbc.edu)
  • In mammalian cells, as many as twenty types of protein have been reported to bind to activated Cdc42 [ 2 ]. (biomedcentral.com)
  • These results uncover a mechanism that couples mTORC2-dependent activation of PKN2 to the regulation of mTORC1-mediated nutrient signalling by local lipid signals. (nature.com)
  • Fig. 2: PKN2 facilitates mTORC1 activation by phosphorylating PI3KC2-β and triggering sequestration by 14-3-3 proteins. (nature.com)
  • Fig. 5: mTORC2 signalling triggers PKN2 activation to control PI3KC2-β phosphorylation and sequestration with 14-3-3 proteins. (nature.com)
  • PKC is involved in the PI-3K-dependent activation of p70 S6K but not MAPK. (nih.gov)
  • In this study, we demonstrate for the first time that GT1b neurotoxicity is accompanied by inactivation of Akt, activation of GSK-3β and increase in tau phosphorylation in mesencephalic DA neurons, both in vivo and in vitro . (biomedcentral.com)
  • Plexin-B1 has recently been shown to mediate activation of RhoA through a stable interaction with the Rho guanine nucleotide exchange factors PDZ-RhoGEF and LARG. (rupress.org)
  • Our data indicate that ErbB-2 is an important component of the plexin-B receptor system and that ErbB-2-mediated phosphorylation of plexin-B1 is critically involved in Sema4D-induced RhoA activation, which underlies cellular phenomena downstream of plexin-B1, including axonal growth cone collapse. (rupress.org)
  • Hormones and growth factors induce the activation of a number of protein kinases that belong to the AGC subfamily, including isoforms of PKA, protein kinase B (also known as Akt), PKC, S6K p70 (ribosomal S6 kinase), RSK (p90 ribosomal S6 kinase) and MSK (mitogen- and stress-activated protein kinase), which then mediate many of the physiological processes that are regulated by these extracellular agonists. (omicsdi.org)
  • The diversified effects of cannabinoids are now known to be mediated through the activation of G-protein-coupled receptors that are normally bound by a family of endogenous ligands, the endocannabinoids ( 1 ). (aacrjournals.org)
  • This creates an environment for increased rapid bioavail ability of E2 which can elicit nongenomic effects such as Ca2 mobilization, kinase activation, and alterations in dopamine subcellular location via membrane estrogen receptors. (inhibitorkit.com)
  • LPLI-induced cell cycle progression can be regulated by the activation or elevated expressions of cell cycle-specific proteins. (biomedcentral.com)
  • Active PKN2 phosphorylates PI3KC2-β to trigger PI3KC2-β complex formation with inhibitory 14-3-3 proteins. (nature.com)
  • It phosphorylates and activates several downstream kinases, including AMP-dependent kinase, AMPK . (sdbonline.org)
  • BIM-1 (GF 109203X) and the related compounds BIM-2, BIM-3, and BIM-8 are bisindolylmaleimide-based protein kinase C (PKC) inhibitors. (wikipedia.org)
  • moreover, PI3′-kinase inhibitors (wortmannin and LY294002) antagonized secretion. (jneurosci.org)
  • By using Akt activity inhibitors, we have mechanistically defined whether the protective effect of RSV on DN was due to Akt-dependent depression of NF- B. (hindawi.com)
  • Modifications Inhibitors,Modulators,Libraries in the phosphorylation state of the DAT by kinases causes alterations in the function and location of the DAT. (inhibitorkit.com)
  • Therefore, we hypothesized Inhibitors,Modulators,Libraries that the estrogen mediated changes in dopamine efflux that we have observed may involve similar mechanisms. (inhibitorkit.com)
  • In this study we exam ined both indirect and direct mechanisms involved in physiological estrogen mediated dopamine efflux in Inhibitors,Modulators,Libraries con junction with the cellular location of the ERs and the DAT. (inhibitorkit.com)
  • This study reports that LKB1 binds to Phosphoinositide-dependent kinase (PDK1) by a conserved binding motif. (sdbonline.org)
  • ERM proteins share a C-terminal actin-binding domain name and an N-terminal FERM domain name that binds to membrane proteins such as CD44 and the axon adhesion molecule L11,2, thereby linking filamentous actin (F-actin) and the membrane to regulate growth cone dynamics3. (estme.org)
  • The PX domain of Vam7p selectively binds PtdIns-3-P, while the PX domain of the CPK PI-3 kinase selectively binds PtdIns-4,5-P(2). (embl.de)
  • KIT is a receptor tyrosine kinase type III, which binds to stem cell factor. (inhibitorkit.com)
  • BI-D1870 is cell permeant and prevents the RSK-mediated phorbol ester- and EGF (epidermal growth factor)-induced phosphoryl-ation of glycogen synthase kinase-3beta and LKB1 in human embry-onic kidney 293 cells and Rat-2 cells. (omicsdi.org)
  • Conversely, loss of PKN2 or inactivation of its target phosphorylation site in PI3KC2-β represses nutrient signalling via mTORC1. (nature.com)
  • Moreover, Akt links a host of upstream signaling molecules to axon development, axon growth, and dendrite NBI-74330 elongation in the central nervous system (CNS) by activating mTORC1 and S6 kinase, which regulate cap-dependent protein translation, and by inhibiting TSC1/224C27. (estme.org)
  • Hepatocyte growth factor receptor (c-Met), a member of tyrosine protein kinase receptors (TPKR), is phosphorylated during LPLI-induced proliferation, but tumor necrosis factor alpha (TNF-alpha) receptor has not been affected. (biomedcentral.com)
  • Raw data for results from screening kinase activity towards T279 of PI3KC2-β are provided in Supplementary Table 2 . (nature.com)
  • In addition to plexins, various other proteins have been implicated either as receptors for semaphorins or as components of the semaphorin receptor complex ( Pasterkamp and Kolodkin, 2003 ). (rupress.org)
  • The IRS proteins function as adaptors and transmit signals from multiple receptors. (scielo.br)
  • Protein phosphorylation of G-protein-coupled receptors (GPCR) is central to the myriad of functions that these ubiquitous receptors perform in biology. (biomedcentral.com)
  • G-protein-coupled receptors (GPCRs) constitute the largest superfamily of cell-surface signaling proteins. (shengsci.com)
  • Outcomes Diet-induced weight problems reduced cardiac blood sugar fat PTK787 2HCl burning capacity GLUT and AMP-activated proteins kinase (AMPK) amounts which was connected with increased degrees of macrophages toll-like receptor 4 suppressor of cytokine signaling 3 (SOCS3) and cytokines in center. (cancer-ecosystem.com)
  • The second messenger PIP3 recruits and activates 3-phosphoinositide dependent protein kinase-1 (PDK1) and AKT serine/threonine kinase on the membrane [ 2 ]. (biomedcentral.com)
  • Upon binding of insulin to the insulin receptor (IR), IRS1 is phosphorylated at several YXXM motifs creating docking sites for the binding of PI3Kp85, which activates AKT kinase. (scielo.br)
  • ERM proteins also act as scaffolds for adaptor and signaling NBI-74330 molecules that regulate cytoskeletal dynamics. (estme.org)
  • This motif is found in Cdc42/Rac-associated proteins such as the protein kinases Pak, MRCK and Ack, the adaptor proteins Spec and WASP, and, in degenerate form, in the kinases MLK, Mekk4, adaptor Par6, scaffold protein IRSp53, and the Borg proteins. (biomedcentral.com)
  • Further, a recent report on the effects of EOPK indicated that the oil has anti-obesity and hypolipidemic activity in vitro and in vivo , using 3 T3-L1 cells and high fat diet-fed rats [ 16 ]. (biomedcentral.com)
  • Moreover, we showed that Acanthamoeba produces severe HBMEC cytotoxicity by secreting extracellular proteases, as well as using contact-dependent mechanisms such as phagocytosis ( 12 ), which may play an important role in blood-brain barrier perturbations. (asm.org)
  • Parafollicular (PF) cells secrete 5-HT in response to stimulation of a G-protein-coupled Ca 2+ receptor (CaR) by increased extracellular Ca 2+ (↑[Ca 2+ ] e ). (jneurosci.org)
  • Further, the contribution of PAK1 to EOPK-induced AKT and extracellular signal-regulated kinase (ERK) suppression was assessed by siRNA-mediated PAK1 knockdown. (biomedcentral.com)
  • The p38 MAPK signaling cascade regulates many cellular functions like the cell routine advancement differentiation apoptosis and irritation dependent on the specific cell type and extracellular stimulus [10]. (health-ground.com)
  • Recently, a large number of signaling proteins reported play an important key role in the process of LPLI-induced cell proliferation, probably due to the fact that the molecular events they are involved in are the basic response of the cells to extracellular stimuli. (biomedcentral.com)
  • Cdc42 and Rac - ancient, highly conserved, small GTPases - mediate extracellular signals, triggering changes in transcription and in the actin cytoskeleton. (biomedcentral.com)
  • p110s perform lipid kinase activity, and p85s stabilize and regulate p110s. (biomedcentral.com)
  • We focus on six 'core' effectors that operate in almost all these species - members of the Pak, WASP/WAVE, formin, lipid-kinase, IQGAP and NADPH oxidase families. (biomedcentral.com)
  • Hypoxia reduces the ability of a cell to maintain its energy level, because less ATP will be obtained from glycolysis than from oxidative phosphorylation. (bmj.com)
  • We suggest that PKC isoforms mediate secretion of 5-HT by PF cells in response to stimulation of the CaR. (jneurosci.org)
  • There are six isoforms of PAK that are classified into two families, Group I (PAK1-3) and Group II (PAK4-6). (biomedcentral.com)
  • Moreover, BI-D1870 does not suppress the phorbol ester- or EGF-induced phosphorylation of CREB (cAMP-response-element-binding protein), consistent with the genetic evidence indicating that MSK, and not RSK, isoforms mediate the mitogen-induced phosphorylation of this transcription factor. (omicsdi.org)
  • However, it is unclear how the activity of plexin-B1 and its downstream effectors is regulated by its ligand Sema4D. (rupress.org)
  • Changes to the expression and phosphorylation of PAK1 and its effectors were determined by western blotting, and changes to the actin cytoskeleton were determined by performing an immunofluorescence assay. (biomedcentral.com)
  • PAKs are downstream effectors of the Rho family GTPases, which regulate cell motility and survival. (biomedcentral.com)
  • The p21-activated kinases (PAKs) are downstream effectors of the Rho family small GTPases as well as a wide variety of mitogenic factors and have been implicated in cancer formation, development and metastasis. (biomedcentral.com)
  • Fig. 1: Serum mitogen-induced phosphorylation of PI3KC2-β induces complex formation with 14-3-3 proteins. (nature.com)
  • Fig. 3: Mitogen starvation-induced recruitment of PI3KC2-β to LyLEs is mediated by its association with Rab7 and is counteracted by PKN2. (nature.com)
  • The mitogen-activated proteins kinases (MAPKs) integrate an array of upstream indicators to determine patterns of downstream gene appearance through the legislation of transcription elements. (health-ground.com)
  • p38 mitogen-activated protein kinase has been implicated in both skeletal muscle atrophy and hypertrophy. (biomedcentral.com)
  • The insulin receptor is a receptor tyrosine kinase (RTK) that conformationally consists of two alpha and two beta subunit tetramers. (encyclopedia.pub)
  • Rather, they show that a major role of hepatic Akt is to restrain the activity of Foxo1 and that in the absence of Foxo1, Akt is largely dispensable for insulin- and nutrient-mediated hepatic metabolic regulation in vivo . (nature.com)
  • Figure 3: Deletion of both Akt1 and Akt2 in liver results in hyperglycemia, glucose intolerance and insulin resistance. (nature.com)
  • Insulin resistance and a diabetes mellitus-like syndrome in mice lacking the protein kinase Akt2 (PKB β). (nature.com)
  • Expression of the mutants differentially affected insulin-induced phosphorylation of IRS1, AKT, ERK, and STAT3. (scielo.br)
  • Following insulin binding, the insulin receptor (IR) autophosphorylates itself and creates docking sites for IRS proteins. (scielo.br)
  • Transfection of cells in culture with ASO targeting PTEN reduced PTEN mRNA and protein levels and increased insulin-stimulated Akt phosphorylation in α-mouse liver-12 (AML12) cells. (diabetesjournals.org)
  • In addition, downregulation of the V-ATPase subunit VhaPPA1-1 reduces Akt and Tor-dependent signaling and restores clearance. (sdbonline.org)
  • It is a catalytic subunit of the protein kinase complex that is important for cell cycle G1 phase progression. (thermofisher.com)
  • and Applied Neurobiology36, 265-274 Immunohistological intensity measurements as a tool to assess sarcolemma-associated protein expression Aims: The quantification of protein levels in muscle biopsies is of particular relevance in the diagnostic process of neuromuscular diseases, but is difficult to assess in cases of partial protein deficiency, particularly when information on protein localization is required. (dehydrogenase-signal.com)
  • Amphetamine, a psychostim ulant, also causes reversal and altered cellular location of the DAT which is known to be regulated by kinases, phos phatases, and Ca2 localization and association. (inhibitorkit.com)
  • Then we addressed the subcellular localization of ER, ER, the alternative mem brane ER, and DAT to see if estrogen induced trafficking of these proteins in and out of the plasma membrane could explain some of the regulatory effects on dopamine efflux. (inhibitorkit.com)
  • such as protein synthesis. (dundee.ac.uk)
  • This study provided evidence that the up-regulation of p27 protein expression is at least in part due to increased synthesis and that this increase fairly faithfully recapitulates the cancer preventive activity of nutritional and chemopreventive anti-cancer agents. (biomedcentral.com)
  • On the other hand, there is growing evidence for the involvement of other lipid metabolites in inducing this metabolic outburst ( 3 - 5 ). (frontiersin.org)
  • Members of a subfamily of these enzymes share a specific domain that was first identified in the yeast Sac1 protein [1]. (embl.de)
  • Tyk2 is a member of the Janus kinase (Jak) subfamily of proteins, which are cytoplasmic (or nonreceptor) tyr kinases containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase domain. (umbc.edu)
  • The master kinase LKB1 is a key regulator of several cellular processes, including cell proliferation, cell polarity and cellular metabolism. (sdbonline.org)
  • This protein is highly similar to the gene products of S. cerevisiae cdc28 and S. pombe cdc2. (thermofisher.com)
  • This kinase was shown to be responsible for the phosphorylation of retinoblastoma gene product (Rb). (thermofisher.com)
  • Mutations in this gene as well as in its related proteins including D-type cyclins, p16(INK4a) and Rb were all found to be associated with tumorigenesis of a variety of cancers. (thermofisher.com)
  • these proteins are also important in regulating gene transcription. (biomedcentral.com)
  • The p21 activated kinase (PAK) family of proteins has been identified as a novel target for cancer therapies [ 7 ]. (biomedcentral.com)
  • However, the Atg8 family of proteins are not found solely attached to double-membrane autophagosomes. (babraham.ac.uk)
  • There are primarily two types of lung cancer: Non-small cell lung cancer (NSCLC) and SCLC, and the former accounts for ~85% of all lung cancer cases ( 3 ). (spandidos-publications.com)
  • Aspartate β-hydroxylase (ASPH) is a type II transmembrane protein and the member of α-ketoglutarate-dependent dioxygenase family, found to be overexpressed in different cancer types, including PC. (bjbms.org)
  • Preliminary studies using either N -methyl- N -nitrosourea (MNU)-induced rat breast cancer model or human breast cancer cell lines in vitro had suggested, but not proved, that nutritional and chemopreventive anti-cancer agents increase p27 protein expression. (biomedcentral.com)
  • While many factors are involved in the etiology of cancer, it has been clearly established that diet significantly impacts risk of this disease [ 1 , 2 , 3 ]. (mdpi.com)
  • The age-adjusted incidence of cancer in the US is 3 times higher than that in Asian countries, with immigrants to the US having increased risk for this condition [ 4 , 5 ]. (mdpi.com)
  • 2004) Akt phosphorylation and gefitinib efficacy in patients with advanced non-small-cell lung cancer. (scielo.br)
  • Furthermore, a PDK1-consensus motif is located within the kinase domain of LKB1 and LKB1 gets phosphorylated by PDK1 in vitro. (sdbonline.org)
  • PF-4708671 was also found to induce phosphorylation of the T-loop and hydrophobic motif of S6K1. (dundee.ac.uk)
  • Various protein kinases are regulating the intracellular signaling network of skeletal muscle cells. (omicsdi.org)
  • We studied the involvement of protein kinases A and C, phospho inositol 3 kinase, extracellu lar regulated kinases , vesicular release of dopamine, and changes in intracellular Ca2 concentra tions in the actions of estrogens. (inhibitorkit.com)
  • Phosphorylation of a PKC induces a conformation leading to import of a PKC into the nucleus. (wikipedia.org)
  • We therefore sought to develop a method to quantify relative levels of sarcolemma-associated proteins using digitally captured images of immunolabelled sections of skeletal muscle. (dehydrogenase-signal.com)
  • The signaling network of skeletal muscle cells is controlled by a variety of protein kinases. (omicsdi.org)
  • Hydroxylation of aspartic acid in domains homologous to the epidermal growth factor precursor is catalyzed by a 2-oxoglutarate-dependent dioxygenase. (bjbms.org)
  • 2005) Activating mutations in the tyrosine kinase domain of the epidermal growth factor receptor are associated with improved survival in gefitinib-treated chemorefractory lung adenocarcinomas. (scielo.br)
  • A study by White et al (2009) found that psychosine's cytotoxic effects on oligodendroglia and Schwann cells was mediated through disruption of the architecture and composition of lipid rafts (cell membrane regions characterized by high cholesterol and sphingolipid concentration), followed by altered protein kinase C (PKC) function. (medscape.com)
  • LKB1 itself is a constitutively active kinase, which is regulated by posttranslational modifications and direct binding to phospholipids of the plasma membrane. (sdbonline.org)
  • Protein modules such as FVYE domains and PH domains that bind specifically to PtdIns 3-phosphate (PtdIns-3-P) and polyphosphoinositides, respectively, can direct such membrane targeting. (embl.de)
  • In addition, the double mutant (Y42A/L48Q) of the PX domain of Vam7p, reported to cause vacuolar trafficking defects in yeast, has a dramatically decreased level of binding to PtdIns-3-P. These data reveal that the membrane targeting function of the Vam7p PX domain is based on its ability to associate with PtdIns-3-P, analogous to the function of FYVE domains. (embl.de)
  • Recent work published in The EMBO Journal and EMBO Reports reveals a novel role for the protein TECPR1 as a sensor for stressed membranes and regulator of lysosomal membrane repair. (babraham.ac.uk)
  • PKC isozymes are LR-dependent molecules that link psychosine-induced LR disruption to reduced PKC function and altered cell signaling activity, possibly driving demyelination and apoptosis in oligodendrocytes and Schwann cells. (medscape.com)
  • A hypoxic environment devoid of nutrients prevents the cell undergoing energy dependent apoptosis and cells become necrotic. (bmj.com)
  • Apoptosis regulatory proteins are delicately balanced. (bmj.com)
  • The key regulator of this process, hypoxia inducible factor 1 (HIF-1), can initiate apoptosis by inducing high concentrations of proapoptotic proteins, such as BNIP3, and can cause stabilisation of p53. (bmj.com)
  • Recently, the signaling proteins involved in LPLI-induced proliferation merit special attention, some of which are regulated by mitochondrial signaling. (biomedcentral.com)
  • In developing neurons, ERM proteins are expressed in growth cones and among ERM proteins, radixin is usually predominant at the leading edge of dorsal root ganglion (DRG) growth cones8,9. (estme.org)
  • Plexins are widely expressed transmembrane proteins that mediate the effects of semaphorins. (rupress.org)
  • Their effects are mediated by plexins, a group of transmembrane proteins. (rupress.org)