PhosphorylationPI3KInhibitorsReceptor tyrosinInhibitor of phosphatidylinositol 3 kinaCytoplasmicInsulin receptorSubstratesPathwayBrutonProteinsInhibitionActivationCatalyticLY294002JanusWortmanninInhibitMutationsP110PhospholipaseExtracellularEnzymesAssayActivatesMembrane-associatedIntracellularRegulatoryGeneGlucoseInositol trisphosphateTumorCascadesProliferation
Phosphorylation31
- Protein tyrosine phosphorylation is an important event in the cell signal transduction process. (nih.gov)
- In this study we have examined the changes in lens protein tyrosine phosphorylation and its impact on phosphatidylinositol 3-kinase (PI-3K) signaling during selenite cataract development. (nih.gov)
- Immunoprecipitation and Western immunoblotting were employed to determine protein tyrosine phosphorylation, PI-3K activity and protein in lens cell extracts. (nih.gov)
- Protein tyrosine phosphorylation in the lens was disrupted before the onset of cataract. (nih.gov)
- A decrease in tyrosine phosphorylation of lens proteins was observed within 2-3 days of selenite injection (pre-cataract stage). (nih.gov)
- The decrease in protein tyrosine phosphorylation correlated with the decrease in tyrosine kinase activity associated with the lens membrane fraction. (nih.gov)
- Stimulation of normal rat lenses in organ culture with insulin and IGF-1 caused an increase in the phosphorylation of proteins, whose tyrosine phosphorylation status appeared to be diminished during cataract development. (nih.gov)
- These studies show that signaling events involving the protein tyrosine phosphorylation process and activation of PI-3K are altered during selenite cataract formation and implicate defects in signal transduction mechanisms as contributing factors in the development of cataract. (nih.gov)
- Phosphorylation of Syk Activation Loop Tyrosines Is Essential for Syk Function. (crossref.org)
- In this work, we report that CD28-mediated cytotoxicity of YT involves tyrosine phosphorylation and activation of phosphatidylinositol (PI) 3-kinase, the Tec kinase Itk/Emt, and protein kinase C (PKC). (elsevierpure.com)
- Taken together, these results are consistent with a model in which activation of CD28 and LFA-1 induces tyrosine phosphorylation of the CD28 cytoplasmic domain, recruitment and activation of PI 3-kinase, as well as the Tec kinase Itk/Emt, and the activation of PMA-nonresponsive PKC isoenzymes. (elsevierpure.com)
- Dive into the research topics of 'CD28-mediated cytotoxicity by the human leukemic NK cell line YT involves tyrosine phosphorylation, activation of phosphatidylinositol 3-kinase, and protein kinase C'. Together they form a unique fingerprint. (elsevierpure.com)
- Erythropoietin induces the tyrosine phosphorylation of insulin receptor substrate-2. (wikipedia.org)
- 1996). "Interleukins 2, 4, 7, and 15 stimulate tyrosine phosphorylation of insulin receptor substrates 1 and 2 in T cells. (wikipedia.org)
- Upon cytokine stimulation, STAT5 tyrosine phosphorylation (pYSTAT5) is transient, while in diverse neoplastic cells persistent overexpression and enhanced pYSTAT5 are frequently found. (nature.com)
- We found that O-GlcNAcylation and tyrosine phosphorylation act together to trigger pYSTAT5 levels and oncogenic transcription in neoplastic cells. (nature.com)
- The expression of a mutated hyperactive gain-of-function (GOF) STAT5 without O-GlcNAcylation resulted in decreased tyrosine phosphorylation, oligomerization and transactivation potential and complete loss of oncogenic transformation capacity. (nature.com)
- Our data show that O-GlcNAcylation of STAT5 is an important process that contributes to oncogenic transcription through enhanced STAT5 tyrosine phosphorylation and oligomerization driving myeloid transformation. (nature.com)
- Cytokine binding to the cell surface leads to phosphorylation of the receptor complex by receptor associated Janus kinases (JAKs) at tyrosine residues. (nature.com)
- 7 The JAKs also trigger the activation and tyrosine phosphorylation of STAT5, causing parallel dimerization, nuclear translocation and tetramerization of STAT5. (nature.com)
- Upon immobilization sAxl advertised cell migration and induced the phosphorylation of Axl and phosphatidylinositol 3-kinase. (exposed-skin-care.net)
- Ang II caused a rapid tyrosine phosphorylation of Src homology and collagen (Shc), which was inhibited by quercetin. (aspetjournals.org)
- CAAX peptidomimetic FTI-244 decreases platelet-derived growth factor receptor tyrosine phosphorylation levels and inhibits stimulation of phosphatidylinositol 3-kinase but not mitogen-activated protein kinase. (nyu.edu)
- Ligand binding to the four closely related members of this RTK family -epidermal growth factor receptor (EGFR, also known as ErbB-1 or HER1), ErbB-2 (HER2), ErbB-3 (HER3), and ErbB-4 (HER4)-induces the formation of receptor homo- and heterodimers and the activation of the intrinsic kinase domain, resulting in phosphorylation on specific tyrosine residues (pY) within the cytoplasmic tail. (genome.jp)
- TLK16998 alone had no effect on IR signaling in mouse 3T3-L1 adipocytes but, at concentrations as low as 3.2 μmol/l, enhanced the effects of insulin on the phosphorylation of the IR β-subunit and IR substrate 1, and on the amount of phosphatidylinositol 3-kinase that coimmunoprecipitated with IRS-1. (diabetesjournals.org)
- Phosphopeptide mapping revealed that the effect of TLK16998 on the IR was associated with increased tyrosine phosphorylation of the activation loop of the β-subunit tyrosine kinase domain. (diabetesjournals.org)
- Here, we showed that hepatocyte growth factor (HGF), a ligand of MET oncoprotein, induces gefitinib resistance of lung adenocarcinoma cells with EGFR -activating mutations by restoring the phosphatidylinositol 3-kinase/Akt signaling pathway via phosphorylation of MET, but not EGFR or ErbB3. (aacrjournals.org)
- The GSK-3, that is the key enzyme is normally showing its actions by various mechanisms that include its phosphorylation, formation of protein complexes, and other cellular distribution and thus it control and directly affects cellular morphology, its growth, mobility and apoptosis of the cell. (scielo.br)
- Exposure to insulin led to tyrosine phosphorylation of the insulin receptor and the insulin-like growth factor-1 (IGF-1) receptor and activation of protein kinase C (PKC) and phosphoinositide 3-kinase (PI3- kinase). (ewha.ac.kr)
- Following B-cell receptor activation, 2 waves of tyrosine kinase phosphorylation occur. (medscape.com)
- Changes in the beta-subunit of the insulin receptor, decreased phosphorylation of tyrosine kinase on the insulin receptor, and alterations in insulin receptor substrate-1 (IRS-1) and the intracytoplasmic phosphatidylinositol 3-kinase (PI3K) appear to be involved in reducing glucose uptake in skeletal muscle tissue. (medscape.com)
PI3K5
- These drugs inhibit Bruton tyrosine kinase (BTK) or phosphatidylinositol 3-kinase (PI3K), key components of the B-cell receptor signaling pathway that is crucial for proliferation, survival and homing of malignant B cells. (haematologica.org)
- PI3K is a cytoplasmic tyrosine kinase involved in various signaling pathways, most importantly activating the AKT/mTOR pathway. (haematologica.org)
- Insulin-induced phosphatidylinositol 3-kinase (PI3K)/Akt signaling and interleukin-6 (IL-6)-instigated JAK/STAT3-signaling pathways in the liver inhibit the expression of gluconeogenic genes to decrease hepatic glucose output. (diabetesjournals.org)
- 42]. Upon BCR stimulation, downstream signaling cascades activate membrane-proximal kinases such as spleen tyrosine kinase (SYK), Bruton tyrosine kinase (BTK) and phosphatidylinositol-3-kinase (PI3K). (nostradamus2018.com)
- SYK Inhibitors Spleen tyrosine kinase (SYK) initiates the BCR signal and is upstream of BTK and PI3K [43]. (nostradamus2018.com)
Inhibitors14
- The lysis was inhibited by two different PI 3-kinase inhibitors, wortmannin and LY294002. (elsevierpure.com)
- Furthermore, exocytosis of cytolytic effector molecules was also inhibited by PI 3-kinase inhibitors and PKC inhibitors. (elsevierpure.com)
- This cytotoxicity displayed by PMA-treated YT cells, however, could still be inhibited by PI 3-kinase inhibitors and PKC inhibitors. (elsevierpure.com)
- moreover, PI3′-kinase inhibitors (wortmannin and LY294002) antagonized secretion. (jneurosci.org)
- Oncogenic protein tyrosine phosphatases have long been viewed as drug targets of interest, and recently developed allosteric inhibitors of SH2 domain-containing phosphatase-2 (SHP2) have entered clinical trials. (aacrjournals.org)
- Collectively, these results suggest that in glioblastoma, SHP2 inhibitors antagonize some signaling processes more effectively than existing kinase inhibitors but can also limit the efficacy of other drugs when used in combination. (aacrjournals.org)
- Lung cancer with epidermal growth factor receptor (EGFR)-activating mutations responds favorably to the EGFR tyrosine kinase inhibitors gefitinib and erlotinib. (aacrjournals.org)
- Targeted approaches to disrupt BCR signaling using Penthiopyrad kinase inhibitors have emerged as an attractive approach in the management of FL (Physique 2). (nostradamus2018.com)
- Inhibitors of tyrosine kinase and PKC, but not PI3-kinase, attenuated the insulin neurotoxicity. (ewha.ac.kr)
- Protein tyrosine kinase inhibitors inhibit both proliferation and chemotaxis of vascular smooth muscle cells. (researchmap.jp)
- Also, the growth-inhibitory effects of HER1/2 tyrosine kinase inhibitors (TKIs) were previously found to be attenuated in the presence of heregulin, which is a high-affinity combinatorial ligand for HER3. (biomedcentral.com)
- However, it appears that regardless of the mechanism that triggers the formation of oncogenic HER2/HER3 heterodimers (HER2 over-expression or overall low HER2 but high levels of the HER3 ligand heregulin), HER3 transphosphorylation is a common response of breast cancer cells upon treatment with current inhibitors of the HER receptor tyrosine kinase network. (biomedcentral.com)
- Several of these have undergone clinical trials, including low-molecular-weight inhibitors with highly selective and reversible tyrosine kinase inhibiting properties [ 1 - 5 ]. (biomedcentral.com)
- Treatment is often supportive, but Janus kinase 2 ( JAK2 ) inhibitors, such as ruxolitinib , fedratinib , pacritnib, or momelotinib may decrease symptoms, and stem cell transplantation may be curative. (msdmanuals.com)
Receptor tyrosin6
- This gene encodes the insulin receptor substrate 2, a cytoplasmic signaling molecule that mediates effects of insulin, insulin-like growth factor 1, and other cytokines by acting as a molecular adaptor between diverse receptor tyrosine kinases and downstream effectors. (wikipedia.org)
- Receptor tyrosine kinases (RTKs) play fundamental tasks in varied cell functions including proliferation differentiation survival migration and rate of metabolism (16). (exposed-skin-care.net)
- The ErbB family of receptor tyrosine kinases (RTKs) couples binding of extracellular growth factor ligands to intracellular signaling pathways regulating diverse biologic responses, including proliferation, differentiation, cell motility, and survival. (genome.jp)
- Although neither kinase-dead human epidermal growth factor receptor (HER)3 nor orphan HER2 can be activated by HER-related ligands on their own, the formation of HER2/HER3 heterodimers creates the most mitogenic and transforming receptor complex within the HER (erbB) family of transmembrane receptor tyrosine kinases. (biomedcentral.com)
- The notion that breast cancer disease can be viewed as a biological process that is driven by overactive human epidermal growth factor receptor (HER)1/2 receptor tyrosine kinases (RTKs) has led to development of various anti-HER tyrosine kinase agents. (biomedcentral.com)
- The receptor tyrosine kinases KIT and FLT3 are both important regulators of development and maintenance of a number of different cell types. (lu.se)
Inhibitor of phosphatidylinositol 3 kina2
- Wortmannin, a fungal metabolite, is a cell-permeable, irreversible inhibitor of phosphatidylinositol 3 kinase (PI3 Kinase) with an IC50 of 5nM. (sigmaaldrich.com)
- Ibrutinib, the first-in-class inhibitor of Bruton tyrosine kinase, and idelalisib, the first-in-class inhibitor of phosphatidylinositol 3-kinase δ , have recently been approved for the treatment of several indolent B-cell malignancies. (haematologica.org)
Cytoplasmic1
Insulin receptor4
- The product of this gene is phosphorylated by the insulin receptor tyrosine kinase upon receptor stimulation, as well as by an interleukin 4 receptor-associated kinase in response to IL4 treatment. (wikipedia.org)
- It blocks the catalytic activity of PI3-Kinase without affecting upstream signaling events such as insulin receptor tyrosine kinase activity. (sigmaaldrich.com)
- The insulin receptor (IR) and JAK1 tyrosine kinases and STAT3 can serve as direct substrates for the T-cell protein tyrosine phosphatase (TCPTP). (diabetesjournals.org)
- Insulin receptor substrates (IRSs) are major targets of IGF-I receptor (IGF-IR) tyrosine kinase activated by IGFs, and are known to play important roles in the activation of downstream signaling pathways, such as the Erk1/2 pathway. (oncotarget.com)
Substrates1
Pathway7
- 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)
- Quercetin also inhibited Ang II-induced Shc·p85 association and subsequent activation of phosphatidylinositol 3-kinase (PI3-K)/Akt pathway in RASMC. (aspetjournals.org)
- The Shc- and/or Grb2-activated mitogen-activated protein kinase (MAPK) pathway is a common target downstream of all ErbB receptors. (genome.jp)
- Similarly, the phosphatidylinositol-3-kinase (PI-3K) pathway is directly or indirectly activated by most ErbBs. (genome.jp)
- Indeed, FL tumors are enriched with T-follicular helper cells (TFH) which highly express IL-4 [45], and dual SYK and Janus kinase (JAK) pathway inhibition can simultaneously target BCR and IL-4 respectively [46]. (nostradamus2018.com)
- Phosphatidylinositol 3-kinase-independent signal transduction pathway for PDGF-induced chemotaxis. (researchmap.jp)
- Although it is kinase defective, the HER family member HER3 can be phosphorylated by HER1 or HER2, and HER3 can couple with the pro-survival phosphatidylinositol-3-OH kinase (PI[ 3 ]K)/Akt pathway directly whereas HER1 and HER2 cannot [ 5 ] (Figure 1 ). (biomedcentral.com)
Bruton1
- the second activates Bruton tyrosine kinase and Syk. (medscape.com)
Proteins2
- While there was no change in total PI-3K activity during the onset of cataract, the activity of PI-3K associated with tyrosine phosphorylated proteins decreased markedly in pre-cataract lenses. (nih.gov)
- These proteins contain pleckstrin homology (PH) domain, and bind SHP2 tyrosine phosphatase and GRB2 adapter protein. (antikoerper-online.de)
Inhibition6
- 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)
- In addition, β-adrenergic-mediated inhibition of PI3 kinase activity was attenuated in SHR (whereas the effect of forskolin remained intact). (aspetjournals.org)
- Protein kinase C-mediated inhibition of vascular smooth muscle cell proliferation : The isoform that may mediate G1/S inhibition. (researchmap.jp)
- Protein kinase C-mediated inhibition of cyclin A expression in human vascular endothelial cells. (researchmap.jp)
- in particular, HER3 signalling buffered against incomplete inhibition of HER2 kinase activity has been suggested to be the mechanism that allows HER2 over-expressing breast cancer cells to escape HER TKIs. (biomedcentral.com)
- Failure to reverse breast cancer progression despite apparent inhibition of HER1 and HER2 kinase functions in cell-based assays as well as in patient tissues and tumours is an enigma that is not yet resolved [ 6 ]. (biomedcentral.com)
Activation9
- Activation of PI 3-kinase and PMA-nonresponsive PKC isoenzymes is shown to be involved directly in cytolytic granule release by YT cells. (elsevierpure.com)
- Ang II-induced cellular events have been implicated, in part, in the activation of mitogen-activated protein (MAP) kinases. (aspetjournals.org)
- Thus, we hypothesized that bioflavonoids may affect Ang II-induced MAP kinase activation in cultured rat aortic smooth muscle cells (RASMC). (aspetjournals.org)
- Our findings showed that Ang II stimulated rapid and significant activation of extracellular signal-regulated kinase (ERK) 1/2, c-Jun N-terminal kinase (JNK), and p38 in RASMC. (aspetjournals.org)
- Ang II-induced JNK activation was inhibited by 3,3′,4′,5,7-pentahydroxyflavone (quercetin), a major bioflavonoid in foods of plant origin, whereas ERK1/2 and p38 activation by Ang II were not affected by quercetin. (aspetjournals.org)
- The non-receptor tyrosine kinase Syk is mainly expressed in the hematopoietic system and plays an essential role in β2 integrin-mediated leukocyte activation. (uni-muenchen.de)
- The protein encoded by this gene is the principal activator of phosphatidylinositol-3 kinase in response to activation of the high affinity IgE receptor. (antikoerper-online.de)
- Therefore, we assessed the effects of β-adrenergic activation on 1) regulation of phosphatidylinositol 3-kinase (PI3 kinase) and extracellular signal-regulated kinase (ERK) activation-two tyrosine kinase-dependent enzymes linked to cell growth-and 2) microarray analysis in vascular smooth muscle cells from spontaneously hypertensive rats (SHR). (aspetjournals.org)
- The activation loop tyrosine 823 is essential for the transforming capacity of the c-Kit oncogenic mutant D816V. (lu.se)
Catalytic1
- PF cells were found to express regulatory (p85) and catalytic (p110α and p110β) subunits of phosphatidylinositol 3′-kinase (PI3′-kinase). (jneurosci.org)
LY2940022
- Acanthamoeba -mediated brain endothelial cell death was abolished using LY294002, a phosphatidylinositol 3-kinase inhibitor. (asm.org)
- Finally, Ang II-induced [ 3 H]leucine incorporation was abolished by both quercetin and LY294002. (aspetjournals.org)
Janus1
- Mutations of the Janus kinase 2 ( JAK2 ) gene are present in a high proportion of cases of primary myelofibrosis. (msdmanuals.com)
Wortmannin2
- Wortmannin, (PI3 Kinase inhibitor) The Wortmannin, (PI3 Kinase inhibitor) controls the biological activity of PI3 Kinase. (sigmaaldrich.com)
- Wortmannin also inhibits the activities of myosin light chain kinase and PI4-Kinase at concentrations a hundred times higher than those required to inhibit PI3-Kinase. (sigmaaldrich.com)
Inhibit1
- Tyrosine kinase ingibitors inhibit multiple steps of the cell cycle of vascular smooth muscle cells. (researchmap.jp)
Mutations2
- Both are linked to transformation due to deregulated kinase/phosphatase signaling or STAT5 gain-of-function (GOF) mutations. (nature.com)
- Deregulation of these tyrosine kinases by mutations has been implicated in various human malignancies, including leukemia and melanoma. (lu.se)
P1101
- The PI3-kinase isoform p110δ is essential for cell transformation induced by the D816V mutant of c-Kit in a lipid-kinase-independent manner. (lu.se)
Phospholipase1
- These include the adaptors Crk, Nck, the phospholipase C gamma (PLCgamma), the intracellular tyrosine kinase Src, or the Cbl E3 ubiquitin protein ligase. (genome.jp)
Extracellular1
- 3 STAT5 regulated signaling controls important functions of innate and acquired immunity, hematopoiesis, and also growth and survival of many cell types in different organs responding to extracellular cytokines. (nature.com)
Enzymes2
- This disease is mainly regulated by various enzymes and hormones among which Glycogen synthase kinase-3 (GSK-3) is a principle enzyme and insulin is the key hormone regulating it. (scielo.br)
- JAK2 is a member of the class I type tyrosine kinase family of enzymes and is involved in signal transduction for erythropoietin , thrombopoietin, and granulocyte colony-stimulating factor (G-CSF) receptors among other entities. (msdmanuals.com)
Assay2
- Description: Using a radiometric protein kinase ( 33 PanQinase activity) assay. (guidetopharmacology.org)
- Routinely evaluated by kinase assay. (sigmaaldrich.com)
Activates1
- Next, we observed that Acanthamoeba specifically activates phosphatidylinositol 3-kinase. (asm.org)
Membrane-associated1
- It encodes a membrane-associated tyrosine kinase that has been implicated in the control of cell growth. (cancerindex.org)
Intracellular1
- Phosphatidylinositol-3 kinase (PI-3K) is an intracellular signal mediator and plays a key role in many cellular functions. (nih.gov)
Regulatory1
- Furthermore, this study supports the hypothesis that the blunting of β-adrenergic responses relating to increased G protein-coupled receptor kinase 2 expression reflects a "generalized uncoupling" of β-adrenergic-mediated responses and do not support the concept of "enhanced coupling" of "alternate" pathways of β-adrenergic growth regulatory pathways in the hypertensive state. (aspetjournals.org)
Gene4
- This gene is a member of the protein-tyrosine kinase oncogene family. (cancerindex.org)
- 3. Kitamura R, Ishii K, Maeda I, Kozaki T, Iwabuchi K, Saito T, Evaluation of bacterial communities by bacteriome analysis targeting 16S rRNA genes and quantitative analysis of ammonia monooxygenase gene in different types of compost. (webmedcentral.com)
- Changes of gene expression by lysophosphatidylcholine in vascular endothelial cells, 12 upregulated distinct genes including 5 cell growth-related, 3 thrombosis-related. (researchmap.jp)
- Protein tyrosines and protein kinase C are required for gene expression of monocyte chemoattractant protein-1 in human monocytes. (researchmap.jp)
Glucose2
- Glycogen synthase kinase-3 (GSK-3) a magic enzyme: it's role in diabetes mellitus and glucose homeostasis, interactions with fluroquionlones. (scielo.br)
- Therefore, it is the need of the day to properly understand functions and mechanisms of GSK-3, especially its role in glucose homeostasis via effects on glycogen synthase. (scielo.br)
Inositol trisphosphate1
- The inositol trisphosphate (IP 3 ) generated by PI-PLC mobilizes Ca 2+ from internal stores ([Ca 2+ ] i ). (jneurosci.org)
Tumor1
- Such IgM+ FL tumor cells efficiently bind dendritic cell-specific intercellular adhesion-3-grabbing nonintegrin (DC-SIGN), a C-type lectin receptor present on the surface of both macrophages and dendritic cells. (nostradamus2018.com)
Cascades1
- They also activate other kinase cascades. (embl.de)