Insulin stimulation of the phosphatidylinositol 3-kinase (PI 3-kinase) pathway, as measured by phosphorylation of the insulin receptor and IRS-1 and by IRS protein association with p85 and with PI 3-kinase, was dramatically reduced in obese nondiabetics and virtually absent in type 2 diabetic patients. (jci.org)
Exercise 24 hours before the euglycemic clamp increased phosphorylation of insulin receptor and IRS-1 in obese and diabetic subjects but did not increase glucose uptake or PI 3-kinase association with IRS-1 upon insulin stimulation. (jci.org)
This process leads to the activation of each receptors' tyrosine kinase and the subsequent phosphorylation of tyrosine residues located on their C-terminal tails. (plos.org)
Protein kinase C (PKC) activator TPA also induced the phosphorylation of p70 S6K. (nih.gov)
Homeodomain-interacting protein kinases (HIPKs) belong to the CMGC kinase family and are closely related to dual-specificity tyrosine phosphorylation-regulated kinases (DYRKs). (nature.com)
HIPKs belong to the CMGC group of serine/threonine kinases and are part of the dual-specificity tyrosine phosphorylation-regulated kinase (DYRK) family. (nature.com)
Phosphorylation of c-jun mediated by MAP kinases. (wikidata.org)
Recent progress in characterization of protein kinase cascades for phosphorylation of ribosomal protein S6. (wikidata.org)
Inhibition of JNK (using SP600125) or small interfering RNA-mediated knockdown of JNK1 blocked acinus formation, impaired cell polarisation and lumen clearance and allowed sustained extracellular signal-regulated kinase (ERK) phosphorylation, cell proliferation, adhesion-independent cell survival and expression of epithelial-mesenchymal transition markers. (ul.ie)
In the present study, we investigated whether contractions of isolated muscles induced phosphorylation of extracellular signal-regulated kinase 1 and 2 (ERK1/2) and p38 MAPK in a fibre-type dependent manner. (elsevierpure.com)
Protein34
RAF kinases are a family of three serine/threonine-specific protein kinases that are related to retroviral oncogenes. (wikipedia.org)
RAF kinases participate in the RAS-RAF-MEK-ERK signal transduction cascade, also referred to as the mitogen-activated protein kinase (MAPK) cascade. (wikipedia.org)
The mitogen-activated protein (MAP) kinases are important signaling molecules that participate in diverse cellular events and are potential targets for intervention in inflammation, cancer, and other diseases. (rcsb.org)
However, the mitogen-activated protein kinase (p42/44 MAPK) cascade inhibitor PD98059 had no effect on p70 S6K activation. (nih.gov)
SP600125 inhibited interleukin-1β-induced JNK activity and activator protein-1 activation, but it did not affect the activation of extracellular-regulated kinase, p38 mitogen-activated protein kinase, and nuclear factor-κB. (aspetjournals.org)
Receptor Tyrosine Kinases (RTKs) and Focal Adhesion Kinase (FAK) regulate multiple signalling pathways, including mitogen-activated protein (MAP) kinase pathway. (gla.ac.uk)
VEGF-induced pMF was attenuated by the MEK/ERK inhibitor U0126 [1,4-diamino-2,3-dicyano-1,4-bis( o -aminophenylmercapto)butadiene] and was abolished by the phosphotidinositol 3 kinase/Akt inhibitor LY294002 [2-(4-morpholinyl)-8-phenyl-1(4 H )-benzopyran-4-one hydrochloride], demonstrating that ERK mitogen-activated protein kinases and Akt are both required for full expression of VEGF-induced pMF. (jneurosci.org)
Homeodomain-interacting protein kinases (HIPKs) are an evolutionarily conserved kinase family comprising the members HIPK1, HIPK2, and HIPK3 in vertebrates, and, additionally, HIPK4 in mammals. (nature.com)
An elevation of the intracellular calcium level, which is mediated by N-methyl-D-aspartate receptors and L-type Ca2+ channels both, activates the mitogen-activated protein (MAP) kinase signaling pathway involved in synaptic modification. (asahq.org)
It has recently been reported that mitogen-activated protein (MAP) kinase (also known as extracellular signal reactive kinase [Erk]) might play an important role in linking membrane depolarization to gene expression in the postsynaptic neurons. (asahq.org)
This study is to investigate the role of p38 mitogen-activated protein kinase (p38MAPK) in tert -butyl hydroperoxide ( t BHP)-induced apoptosis of human trabecular meshwork (iHTM) cells. (molvis.org)
Mitogen-activated protein kinases (MAPKs) comprise a large family of proteins activated by a wide range of proinflammatory cytokines and environmental stress. (molvis.org)
Mitogen-activated protein kinase 9 OS=Oryza sativa subsp. (cornell.edu)
Rapid and transient activation of myelin basic protein kinase in tobacco leaves treated with hairpin from Erwinia amylovora . (springer.com)
The mitogen-activated protein kinase (MAPK) cascade is a highly conserved module that is involved in various cellular functions, including cell proliferation, differentiation and migration. (wikipathways.org)
A screen profiling 158 kinase inhibitors (Calbiochem Protein Kinase Inhibitor Library I and II, catalogue numbers 539744 and 539745) for their inhibitory activity at 1µM and 10µM against 234 human recombinant kinases using the EMD Millipore KinaseProfiler TM service. (guidetopharmacology.org)
A screen profiling the inhibitory activity of 178 commercially available kinase inhibitors at 0.5µM against a panel of 300 recombinant protein kinases using the Reaction Biology Corporation Kinase Hotspot SM platform. (guidetopharmacology.org)
A putative protein kinase overcomes pheromone-induced arrest of cell cycling in S. cerevisiae. (wikidata.org)
Muscle proteins related to microtubule associated protein-2 are substrates for an insulin-stimulatable kinase. (wikidata.org)
Insulin-stimulated MAP-2 kinase phosphorylates and activates ribosomal protein S6 kinase II. (wikidata.org)
Fission yeast genes that confer resistance to staurosporine encode an AP-1-like transcription factor and a protein kinase related to the mammalian ERK1/MAP2 and budding yeast FUS3 and KSS1 kinases. (wikidata.org)
Protein kinase C regulates human pluripotent stem cell self-renewal. (rndsystems.com)
Identification of a novel inhibitor of mitogen-activated protein kinase kinase. (rndsystems.com)
To do so, we mutated the proteolytically revealed TL sequence of rPAR 2 and examined the impact on stimulating intracellular calcium transients and mitogen-activated protein (MAP) kinase. (aspetjournals.org)
David H Shepp, MD Associate Professor of Medicine Zucker School of Medicine at Hofstra-Northwell Manhasset, NY - (03/13/18) - Understanding how protein kinases deliver intracellular activation signals to regulate growth, and development of drugs to block them, has revolutionized the treatment of certain cancers and rheumatologic disorders. (natap.org)
There are many different protein kinases utilized by the major classes of cytokine receptors to deliver intracellular activation signals. (natap.org)
Endometrial ( EN ) and placental ( PL ) morphology and protein synthesis during pregnancy ( PG ) and pseudopregnancy ( PS ) in the cat. (anl.gov)
Over the last few decades, it has been studied that the mechanisms of cisplatin-induced kidney damage are complex and involved numerous cellular and molecular processes including inflammation, apoptosis, accumulation of cisplatin in renal tubular cells via renal drug transporters, Ctr1 and OCT2, and involvement of mitogen-activated protein kinases (MAPK) pathways [ 3 ] [ 4 ]. (thieme-connect.com)
Activation of mitogen-activated protein (MAP) kinases has been implicated in the signal transduction pathways linking exercise to adaptive changes of muscle protein expression. (elsevierpure.com)
GS-002 also induced endoplasmic reticular (ER) stress as evidenced by increases in ER stress-responsive proteins including glucose-regulated protein 78 (GRP78), growth arrest- and DNA damage-inducible gene 153 (GADD153), phosphorylated eukaryotic initiation factor 2 α (eIF2 α ), phosphorylated protein endoplasmic-reticular-resident kinase (PERK), and ATF-3. (hindawi.com)
The induction of ATF-3 expression was mediated by mitogen-activated protein kinase (MAPK) signaling pathways in GS-002-treated cells. (hindawi.com)
Image analysis of the matched maps identified 7 proteins that were either over- or down-expressed: activated protein kinase c receptor (LACK), alpha tubulin (×2), prostaglandin f2-alpha synthase, protein disulfide isomerase, vesicular transport protein and a hypothetical protein. (who.int)
Mathematical modeling of signal transduction networks has previously been used to map out thermodynamical using rate equations is increasingly attracting attention as a properties of protein-folding models (6,7). (lu.se)
Inhibitor8
We here evaluated the effects of SP600125 (anthra[1,9- cd ]pyrazole-6 (2 H )-one), an inhibitor of c-Jun NH 2 -terminal kinase (JNK), on the activation of PSCs. (aspetjournals.org)
The expression of c-Fos induced by potassium chloride was also suppressed by dibucaine, tetracaine (concentrations that inhibited 50% of the activity of positive control [IC50s] were 16.2+/-0.2 and 73.2+/-0.7 microM, respectively), and PD 98059, a mitogen-activated/extracellular receptor-regulated kinase inhibitor. (asahq.org)
The human trabecular meshwork cells were treated with t BHP for 1 or 2 h with or without pretreatment of SB203580, an inhibitor of MAP kinase homologs. (molvis.org)
1. Anastassiadis T, Deacon SW, Devarajan K, Ma H, Peterson JR. (2011) Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity. (guidetopharmacology.org)
U0126 is a potent and selective non-competitive inhibitor of MAP kinase kinase. (rndsystems.com)
presented the effects of an investigational p38 MAP kinase inhibitor (PH797804) combined with ART in SIV-infected macaques (Aldovini A, abstract 20). (natap.org)
Rhesus macaques were infected with SIVmac251 and divided in 6 groups: Group 1, had no treatment, Group 2, p38 inhibitor alone, Groups 3 and 5 initiated ART at week 6 or 1 after infection, Group 4 and 6 initiated ART + PH797804 at week 6 or 1 after infection. (natap.org)
Previous studies reported that ATF-3 was induced by treating cells with antitumorigenic compounds [ 14 - 18 ] and a phosphoinositide 3-kinase inhibitor [ 19 ]. (hindawi.com)
Pathway10
Insulin stimulation of the MAP kinase pathway was normal in obese and diabetic subjects. (jci.org)
The MAP-kinase pathway is a major pathway in relaying signals from the plasma membrane into the nucleus. (europa.eu)
Because the effects of local anesthetics on cellular signal transduction in neuronal cells are not well-known, the authors investigated whether they affect the MAP kinase signaling pathway using PC12 cells. (asahq.org)
Although probable targets of these local anesthetics might be L-type Ca2+ channels or components between Ca2+ and Ras in MAP kinase pathway, the possibility that they directly affect MAP kinase still remains. (asahq.org)
The suppression of MAP kinase pathway may thus be a potential target site for the actions of dibucaine and tetracaine, including the modification of the synaptic functions. (asahq.org)
Choline kinase (ChoK), the enzyme responsible for the generation of phosphorylcholine (PCho) from its precursor choline, is the first enzyme in the Kennedy pathway that renders phosphatidylcholine as its final product. (aacrjournals.org)
There is evidence that cell proliferation in Spitz nevi, as in other types of nevi and in melanoma, is primarily mediated by activating mutations affecting genes in the RAS-RAF-MEK-ERK-MAP kinase pathway. (medscape.com)
In particular, extracellular-regulated kinase (ERK) 1/2, one of the MAPK pathway is considered as an important mediator of signal transduction processes, namely cell survival, cell division, gene expression, and cell metabolism that plays role in injury, death, and inflammation of kidney tubular cells due to cisplatin administration [ 5 ]. (thieme-connect.com)
In breast cancer, ATF-3 enhances cancer cell-initiating features [ 22 ] and is associated with activation of the canonical Wnt/ β -catenin pathway [ 23 ]. (hindawi.com)
The first piece of information, which was a little surprising, was that there was no significant impact of any of the mutations on outcome, including the BRAF amplifications, mutations in the MAP kinase pathway, or MEK1/2 mutations. (medscape.com)
Pathways4
Thus, insulin resistance differentially affects the PI 3-kinase and MAP kinase signaling pathways, and insulin-stimulated IRS-1-association with PI 3-kinase defines a key step in insulin resistance. (jci.org)
In conclusion, MAP kinase signalling pathways are differentially activated and expressed in slow- and fast-twitch muscles. (elsevierpure.com)
These results suggest that the induction of apoptosis by the propolis derivative, GS-002, is partially mediated through ER stress and ATF-3-dependent pathways, and GS-002 has the potential for development as an antitumor drug. (hindawi.com)
Tyrosine12
Nuclear localized HER family receptor tyrosine kinases (RTKs) have been observed in primary tumor specimens and cancer cell lines for nearly two decades. (plos.org)
Results from these analyses demonstrated that the C-terminal domain of HER3 (CTD, amino acids distal to the tyrosine kinase domain) contained potent transactivation potential. (plos.org)
Brand TM, Iida M, Luthar N, Wleklinski MJ, Starr MM, Wheeler DL (2013) Mapping C-Terminal Transactivation Domains of the Nuclear HER Family Receptor Tyrosine Kinase HER3. (plos.org)
The ErbB/HER family of receptor tyrosine kinases (RTKs) consists of four family members: the epidermal growth factor receptor (EGFR/ErbB1), HER2 (ErbB2/Neu), HER3 (ErbB3), and HER4 (ErbB4). (plos.org)
VEGFA-165 signals by activating its receptor tyrosine kinase VEGF receptor-2 (VEGFR-2). (jneurosci.org)
Because another growth/trophic factor that signals via a receptor tyrosine kinase (brain derived neurotrophic factor) elicits a long-lasting facilitation of respiratory motor activity in the phrenic nerve, we tested the hypothesis that VEGFA-165 elicits similar phrenic motor facilitation (pMF). (jneurosci.org)
For the class II DYRK ortholog from D. melanogaster it was demonstrated that the critical tyrosine is cis -auto-phosphorylated by the nascent kinase in a transitory intermediate state during maturation at the ribosome 3 . (nature.com)
X-linked agammaglobulinemia (XLA), or Bruton agammaglobulinemia, is an inherited immunodeficiency disease caused by mutations in the gene coding for Bruton tyrosine kinase (BTK). (medscape.com)
The BTK gene defect has been mapped to the long arm of the X chromosome at band Xq21.3 to Xq22, spanning 37.5kb with 19 exons forming 659 amino acids to complete the BTK cytosolic tyrosine kinase. (medscape.com)
Inhibitors4
The anti-inflammatory agent pyridinylimidazole and its analogs (SB [SmithKline Beecham] compounds) are highly potent and selective inhibitors of p38, but not of the closely-related ERK2, or other serine/threonine kinases. (rcsb.org)
2010) Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry. (guidetopharmacology.org)
No p38 MAP kinase inhibitors are approved for clinical use, but several are being investigated in other diseases. (natap.org)
Serine2
C-terminally adjacent to the HID follows a proline, glutamate, serine, and threonine (PEST)-rich domain, mediating proteasomal degradation of these kinases. (nature.com)
Finally, the C-terminus of HIPK1-3 comprises a region rich in serine, glutamine, and alanine (SQA) residues, which is involved in the interaction with different co-factors 14 . (nature.com)
This family of RTKs has been highly implicated in the formation and progression of various cancers via aberrant overexpression, kinase activation, and mutation [1] , [2] . (plos.org)
In contrast, the activation of the MAP kinase ERK2 (extracellular-signal-regulated kinase 2) leads to cellular differentiation or proliferation. (rcsb.org)
Pretreatment of the cells with 1 mM (ethylenedioxy)-diethyl-enedinitrilotetraacetic acid or 5 micron nifedipine blocked the MAP kinase activation induced by 50 mM KCl, whereas pretreatment with 2 microM omega-conotoxin GIVA did not. (asahq.org)
Higher concentrations of dibucaine and tetracaine were needed to suppress the activation of MAP kinase induced by ionomycin (the IC50 values of dibucaine and tetracaine were 62.5+/-2.2 and 330.5+/-32.8 microM, respectively) compared with potassium chloride (the IC50 values of dibucaine and tetracaine were 17.7+/-1.0 and 70.2+/-1.2 microM, respectively). (asahq.org)
Dibucaine and tetracaine at clinical concentrations were found to inhibit the activation of MAP kinase and the expression of c-Fos mediated by L-type Ca2+ channels in PC12 cells. (asahq.org)
Choline kinase (ChoK) is increased in human mammary tumors with high incidence, and this activation is associated with clinical variable indicators of greater malignancy. (aacrjournals.org)
Type IV secretion-dependent activation of host MAP kinases induces an increased proinflammatory cytokine response to Legionella pneumophila. (nih.gov)
Upon trypsin activation, all constructs stimulated MAP kinase signaling, but only the wt-rPAR 2 and rPAR 2 -Ala 39-42 triggered calcium signaling. (aspetjournals.org)
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)
Hyperglycemia induced by glucose infusion causes hepatic oxidative stress and systemic inflammation, but not STAT3 or MAP kinase activation in liver in rats. (bidmc.org)
Activation of MAP kinases by hexavalent chromium, manganese and nickel in human lung epithelial cells. (cdc.gov)
Phosphorylates and activates1
It phosphorylates and activates several downstream kinases, including AMP-dependent kinase, AMPK . (sdbonline.org)
Proteins1
Mammals express at least four distinctly regulated groups of MAPKs, extracellular signal-related kinases (ERK)-1/2, Jun amino-terminal kinases (JNK1/2/3), p38 proteins (p38alpha/beta/gamma/delta) and ERK5, that are activated by specific MAPKKs: MEK1/2 for ERK1/2, MKK3/6 for the p38, MKK4/7 (JNKK1/2) for the JNKs, and MEK5 for ERK5. (wikipathways.org)
Phosphoinositide1
This study reports that LKB1 binds to Phosphoinositide-dependent kinase (PDK1) by a conserved binding motif. (sdbonline.org)
ERK12
Detects endogenous levels of human p42 and p44 MAP kinase (Erk1 and Erk2) only when phosphorylated either individually or dually at Thr202 and Thr204 of Erk1 (Thr185 an Tyr187 of Erk2). (lsbio.com)
Does not cross-react with the corresponding phosphorylated residues of either JNK/SAPK or p38 MAP kinase, or non-phosphorylated Erk1/2. (lsbio.com)
Melanoma1
These kinase fusions represent partial transformation towards potential melanoma as well as potential therapeutic targets for metastatic melanoma harboring these kinase fusions. (medscape.com)
Cytokine1
Pathophysiologically, asthma exert different effects at different concentrations, can is characterized by constriction of airway smooth synergize or antagonize the effects of other cytokines muscle, hyper secretion of mucus, edema and airway and regulated in a complex manner and function via hyper responsiveness (AHR),[3] mucus secretion and cytokine cascade. (cdc.gov)
Receptor3
The current study aimed to map the putative transactivation domains (TADs) of the HER3 receptor. (plos.org)
Classically, HER family members function from the cell surface, where binding to cognate ligands can induce receptor homo- or hetero-dimerization with other HER family receptors [3] . (plos.org)
However, restricted feeding in Holstein bull calves in the first 3 wk of life reduced average daily gain (ADG) and resulted in bulls that were lighter and had lower testosterone concentrations at 10 wk, than calves fed and and gene expression starts reducing with enhanced androgen receptor (and in mice, lowered Sertoli cell proliferation, resulting in 70% reduction in testes size. (forgetmenotinitiative.org)
Signals1
The peptides AAIGRL-NH 2 and LSIGRL-NH 2 triggered neither calcium nor MAP kinase signals. (aspetjournals.org)
Differentially2
At 24 wk, a total of 87 genes were differentially expressed (Supplementary dataset?3), with 41 upregulated in high-diet bulls (genes with higher log2fold change- KRT8, ENPP3, CA3, HSD17B3). (forgetmenotinitiative.org)
Desk 3 Primer sequences useful for validation of indicated genes in the testicular cells of Holstein bull calves differentially. (forgetmenotinitiative.org)
Gene2
It has recently been suggested that MAP kinase plays a role in coupling the synaptic excitation to gene expression in the nucleus of postsynaptic neurons. (asahq.org)
ATF-3 induces DNA synthesis and expression of cyclin D1 in hepatocytes [ 21 ] and is involved in serum-induced cell proliferation as a target gene of c-myc [ 10 ]. (hindawi.com)
Mutation1
No single mutation accounts for more than 3% of mutations in patients. (medscape.com)
Receptors2
5 MAP kinase has been shown to be activated by calcium influx through both N -methyl-D-aspartate (NMDA) receptors and L-type Ca 2+ channels. (asahq.org)
Furthermore, the TL-derived synthetic peptide SLAAAA-NH 2 failed to cause PAR 2 -mediated calcium signaling but did activate MAP kinase, whereas SLIGRL-NH 2 triggered both calcium and MAP kinase signaling by all receptors. (aspetjournals.org)
Mutants2
Next, nine HER3-CTD truncation mutants were constructed to map minimal regions of transactivation potential using the Gal4 UAS-luciferase based system. (plos.org)
Mutants lacking the MAP kinase DdERK2 show reduced chemotactic responses to folate and cAMP. (elsevierpure.com)
Assay1
Cell viability was analyzed using 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2h-tetrazolium bromide assay. (molvis.org)
Inhibition1
These studies suggest inhibition or p38 MAP kinase should be explored as an adjunct to ART in HIV. (natap.org)
20231
Deniz, O , Hasygar, K & Hietakangas, V 2023, ' Cellular and physiological roles of the conserved atypical MAP kinase ERK7 ', FEBS Letters , Vuosikerta 597, Nro 5, Sivut 601-607. (helsinki.fi)
BRAF1
Spitz nevi (as well as as atypical Spitz tumors and spitzoid melanomas) frequently harbor kinase fusions (ROS1, NTRK1, ALK, BRAF, RET, MET) in mutually exclusive pattern. (medscape.com)
Sequence2
Within the HIPK family, HIPK1 and HIPK2 are the most closely related members, sharing about 93% sequence identity in their kinase domains, while HIPK3 is slightly less conserved with 87% identity. (nature.com)
No member sequence or clone is mapped. (cornell.edu)
Epithelial1
Primary murine mammary epithelial cells cultured on a laminin-rich-extracellular matrix (ECM) require c-Jun N-terminal kinase (JNK) activity for acinus formation. (ul.ie)
Caspase2
In HL-60 leukaemia cells, di-GA activated caspase 3 and dose-dependently induced apoptosis. (nature.com)
Several main apoptotic indicators were found in GS-002-treated cells, such as the cleaved forms of caspase-3, caspase-9, and poly(ADP-ribose) polymerase (PARP). (hindawi.com)