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  • mammalian
  • Moreover, PI3K and Akt inhibitors, but not mammalian target of rapamycin inhibitor, inhibited the effect of insulin on the coprecipitation of procaspase-9 and XIAP. (aacrjournals.org)
  • Mammalian Clk/Sty is the prototype for a family of dual specificity kinases (termed LAMMER kinases) that have been conserved in evolution, but whose physiological substrates are unknown. (semanticscholar.org)
  • The mechanistic target of rapamycin (mTOR), also known as the mammalian target of rapamycin and FK506-binding protein 12-rapamycin-associated protein 1 (FRAP1), is a kinase that in humans is encoded by the MTOR gene. (wikipedia.org)
  • That of FKBP12-rapamycin remained mysterious until genetic and molecular studies in yeast established FKBP12 as the target of rapamycin, and implicated TOR1 and TOR2 as the targets of FKBP12-rapamycin in 1991 and 1993, followed by studies in 1994 when several groups, working independently, discovered the mTOR kinase as its direct target in mammalian tissues. (wikipedia.org)
  • Mammalian ROCK consists of a kinase domain, a coiled-coil region and a Pleckstrin homology (PH) domain, which reduces the kinase activity of ROCKs by an autoinhibitory intramolecular fold if RhoA-GTP is not present. (wikipedia.org)
  • pathway
  • The differential effects of the MEK inhibitors on cell survival were not dependent on p53 status or effects on the ERK5 pathway. (aspetjournals.org)
  • The studies revealed individual elements of the phototropin-dependent signal transduction pathway involved in the blue-light-controlled change in chemotaxis mode of C. reinhardtii during gamete formation: three protein kinases, one operating against signal flux and two that promote signal transduction. (mdpi.com)
  • Analysis of the signaling pathway by which light controls the conversion of pregametes to gametes using pharmacological compounds suggests the participation of protein kinases and cAMP in this signaling cascade [ 15 ]. (mdpi.com)
  • The pathway involving the cyclic guanosine-3′,5′-monophosphate (cGMP) may provide a unique signaling mechanism in regulating axon branching. (jneurosci.org)
  • The MAP kinase pathway could be overactive in a proportion of lung cancers, including some which also have another mutation in a protein known as KRAS (Kirsten rat sarcoma viral oncogene homolog). (clinicaltrials.gov)
  • Signalling pathway for RKIP and Let-7 regulates and predicts metastatic breast cancer. (labome.org)
  • Because of these different names, mTOR, which had been first used by Robert T. Abraham, was increasingly adopted by the community of scientists working on the mTOR pathway to refer to the protein and in homage to the original discovery of the TOR protein in yeast that was named TOR, the Target of Rapamycin, by Joe Heitman, Rao Movva, and Mike Hall. (wikipedia.org)
  • 2001
  • The farnesyltransferase inhibitors were developed from biochemical experiments on H-Ras proteins, and it is likely that K-Ras (and perhaps also N-Ras) proteins can be alternatively modified by geranylgeranylation when farnesyltransferase activity is blocked ( Adjei, 2001 ). (aspetjournals.org)
  • Regulation
  • However, in recent years, new evidence proved that the presence of CDK6 is not essential for proliferation in every cell type, the cell cycle has a complex circuitry of regulation and the role of CDK6 might be more important in certain cell types than in others, where CDK4 or CDK2 can act as protein kinases compensating its role. (wikipedia.org)
  • mTORC2 is activated by growth factors, phosphorylates PKCα, AKT and paxillin, and regulates the activity of the small GTPase, Rac, and Rho related to cell survival, migration and regulation of the actin cytoskeleton. (wikipedia.org)
  • However, there are many illnesses caused by down-regulation of eIF2 through its upstream kinases. (wikipedia.org)
  • centrosome separation
  • Protein kinase which is involved in the control of centrosome separation and bipolar spindle formation in mitotic cells and chromatin condensation in meiotic cells. (wikipedia.org)
  • Regulates centrosome separation (essential for the formation of bipolar spindles and high-fidelity chromosome separation) by phosphorylating centrosomal proteins such as CROCC, CEP250 and NINL, resulting in their displacement from the centrosomes. (wikipedia.org)
  • 1996
  • These molecular cues have positive or negative effects on growth cone motility as they bind to surface receptors and trigger intracellular pathways that regulate cytoskeletal components underlying growth cone motility ( Letourneau, 1996 ). (jneurosci.org)
  • cellular
  • Regulating the cleavage of various caspases by survival factors is therefore essential for the cellular balance between survival and death. (aacrjournals.org)
  • Cyclic GMP has been proposed to regulate axonal development, but the molecular and cellular mechanisms underlying the formation of axon branches are not well understood. (jneurosci.org)
  • These results identify the first molecule, myosin II, which directly regulates cellular patterning and alignment within the cochlear sensory epithelium. (biologists.org)
  • The mechanisms that regulate elongation of the duct and/or cellular patterning within the OC are largely unknown. (biologists.org)
  • ABC proteins transport various molecules across extra- and intra-cellular membranes. (wikipedia.org)
  • mTOR links with other proteins and serves as a core component of two distinct protein complexes, mTOR complex 1 and mTOR complex 2, which regulate different cellular processes. (wikipedia.org)
  • The two natural products were used to discover the FK506- and rapamycin-binding proteins, including FKBP12, and to provide evidence that FKBP12-FK506 and FKBP12-rapamycin might act through gain-of-function mechanisms that target distinct cellular functions. (wikipedia.org)
  • mTOR regulates cellular metabolism, growth, and proliferation by forming and signaling through two protein complexes, mTORC1 and mTORC2. (wikipedia.org)
  • ROCK plays a role in a wide range of different cellular phenomena, as ROCK is a downstream effector protein of the small GTPase Rho, which is one of the major regulators of the cytoskeleton. (wikipedia.org)
  • Cellular contractility ROCK also regulates cell migration by promoting cellular contraction and thus cell-substratum contacts. (wikipedia.org)
  • receptors
  • Currently there are several drugs launched or in development that target protein kinases and the receptors that activate them: Note: AD = Approval date. (wikipedia.org)
  • As a core component of mTORC2, mTOR also functions as a tyrosine protein kinase that promotes the activation of insulin receptors and insulin-like growth factor 1 receptors. (wikipedia.org)
  • complexes
  • The protein can be found in the cytoplasm and the nucleus, however most of the active complexes are found in the nucleus of proliferating cells. (wikipedia.org)
  • Importantly, these C-CDK complexes act as a kinase, phosphorylating and inactivating the protein of Rb and p-Rb related "pocket proteins" p107 and p130. (wikipedia.org)
  • SCF complexes consist of four proteins: Rbx1, Cul1, Skp1, which are invariant among SCF complexes, and an F-box protein, which varies. (wikipedia.org)
  • These two complexes have a separate network of protein partners, feedback loops, substrates, and regulators. (wikipedia.org)
  • myosin
  • Non-muscle myosin 2 (NM II) is a hexameric protein composed of two dimeric heavy chains (NMHCs), a pair of regulatory light chains (RLCs) and a pair of essential light chains. (biologists.org)
  • caspase
  • In type I cells, active caspase-8 directly cleaves downstream procaspase-3 (9) , whereas a small amount of caspase-8 activated in type II cells truncates the BH3 domain-containing proapoptotic Bcl-2 family protein (BID). (aacrjournals.org)
  • Cell death was preceded by DNA synthesis inhibition and G 1 -G 2 arrest, reversed by the pancaspase inhibitor, zVAD-fmk, and associated with caspase-3 and -2 activation and CytC increase. (aacrjournals.org)
  • The pro-apoptotic protease, caspase 3, activates ROCK kinase activity by cleaving the C-terminal PH domain. (wikipedia.org)
  • cell
  • Individual MEK inhibitors had similar effects in all three cell lines. (aspetjournals.org)
  • A specific inhibitor of endothelial cell growth and angiogenesis. (sigmaaldrich.com)
  • 2-Methoxyestradiol (2-ME) is a potent inhibitor of endothelial cell proliferation and angiogenesis. (sigmaaldrich.com)
  • P-glycoprotein 1 (permeability glycoprotein, abbreviated as P-gp or Pgp) also known as multidrug resistance protein 1 (MDR1) or ATP-binding cassette sub-family B member 1 (ABCB1) or cluster of differentiation 243 (CD243) is an important protein of the cell membrane that pumps many foreign substances out of cells. (wikipedia.org)
  • Ubiquitination by E3 ligases regulates diverse areas such as cell trafficking, DNA repair, and signaling and is of profound importance in cell biology. (wikipedia.org)
  • Several downstream pathways that regulate cell-cycle progression, translation, initiation, transcriptional stress responses, protein stability, and survival of cells are signaling through mTOR. (wikipedia.org)
  • ROCKs regulate cell-cell adhesion: Loss of ROCK activity seems to lead to loss of tight junction integrity in endothelial cells. (wikipedia.org)
  • The protein is highly conserved among evolutionary remote species - indicating a large impact of mutations on cell viability. (wikipedia.org)
  • This protein is indirectly involved in the non-cell autonomous inhibitory effect on fibroblast growth factor two signaling. (wikipedia.org)
  • mechanism
  • E3 ubiquitin ligases catalyze polyubiquitination events much in the same way as the single ubiquitylation mechanism, using instead a lysine residue from a ubiquitin molecule currently attached to substrate protein to attack the C-terminus of a new ubiquitin molecule. (wikipedia.org)
  • The discovery of mTOR was made a few decades ago while investigating the mechanism of action of its inhibitor, rapamycin. (wikipedia.org)
  • Induces
  • The 43S PIC and the eIF4F proteins form a new 48S complex on the mRNA, which starts searching along the mRNA for the start codon (AUG). Upon base pairing of the AUG-codon with the Met-tRNA, eIF5 (which is a GTPase-activating protein) is recruited to the complex and induces eIF2 to hydrolyse its GTP. (wikipedia.org)
  • activity
  • At the molecular level, the cGMP-dependent protein kinase 1 (PrkG1) mediates this activity, as DRG neurons isolated from the kinase-deficient mouse fail to respond to cGMP activation to make branches, whereas overexpression of a PrkG1 mutant with a higher-than-normal basal kinase activity is sufficient to induce branching. (jneurosci.org)
  • We also demonstrate the requirement of PrkG1 and reveal that its kinase activity is both necessary and sufficient for this function. (jneurosci.org)
  • Conti and Adelstein, 2008 ), regulates self-assembly and ATPase activity ( Conti and Adelstein, 2008 ). (biologists.org)
  • Kv1.3 potassium channel mediates macrophage migration in atherosclerosis by regulating ERK activity. (sigmaaldrich.com)
  • A 2015 review of polymorphisms in ABCB1 found that "the effect of ABCB1 variation on P-glycoprotein expression (messenger RNA and protein expression) and/or activity in various tissues (e.g. the liver, gut and heart) appears to be small. (wikipedia.org)
  • There are additional functions of CDK6 not associated with its kinase activity. (wikipedia.org)
  • These substrates, once phosphorylated, regulate actin filament organization and contractility as follows: Amount of actin filaments ROCK inhibits the depolymerization of actin filaments indirectly: ROCK phosphorylates and activates LIM kinase, which in turn phosphorylates ADF/cofilin, thereby inactivating its actin-depolymerization activity. (wikipedia.org)
  • U0126 was found to functionally antagonize AP-1 transcriptional activity via noncompetitive inhibition of the dual specificity kinase MEK with IC50 of 72 nM for MEK1 and 58 nM for MEK2. (wikipedia.org)
  • MEK inhibitors: The chemistry and biological activity of U0126, its analogs, and cyclization products. (wikipedia.org)
  • The encoded protein contains a carboxyl-terminal cysteine-rich domain essential for the inhibitory activity on receptor tyrosine kinase signaling proteins and is required for growth factor stimulated translocation of the protein to membrane ruffles. (wikipedia.org)
  • enzyme
  • A protein kinase inhibitor is a type of enzyme inhibitor that blocks the action of one or more protein kinases. (wikipedia.org)
  • A ubiquitin ligase (also called an E3 ubiquitin ligase) is a protein that recruits an E2 ubiquitin-conjugating enzyme that has been loaded with ubiquitin, recognizes a protein substrate, and assists or directly catalyzes the transfer of ubiquitin from the E2 to the protein substrate. (wikipedia.org)
  • In enzymology, an ubiquitin-protein ligase (EC 6.3.2.19) is an enzyme that catalyzes the chemical reaction ATP + ubiquitin + protein lysine ⇌ {\displaystyle \rightleftharpoons } AMP + diphosphate + protein N-ubiquityllysine The 3 substrates of this enzyme are ATP, ubiquitin, and a lysine residue on a protein, whereas its 3 products are AMP, diphosphate, and protein N-ubiquityllysine. (wikipedia.org)
  • The systematic name of this enzyme class is ubiquitin:protein-lysine N-ligase (AMP-forming). (wikipedia.org)
  • The E2 enzyme interacts with a specific E3 partner and transfers the ubiquitin to the target protein. (wikipedia.org)
  • interaction
  • Growth cones of sensory axons are probably regulated by interaction of cytoplasmic signaling triggered coincidentally by both types of guidance molecules. (jneurosci.org)
  • amino
  • It appears that growth factors, amino acids, ATP, and oxygen levels regulate mTOR signaling. (wikipedia.org)
  • The sequences of all three sub-units are highly conserved (pairwise amino acid identities for each sub-unit range from 47-72% when comparing the proteins of Homo sapiens and Saccharomyces cerevisiae). (wikipedia.org)
  • Those kinases act as a result of stress such as amino acid deprivation (GCN2), ER stress (PERK), the presence of dsRNA (PKR) heme deficiency (HRI), or interferon. (wikipedia.org)
  • Furthermore, low concentration of ternary complex allows the expression of GCN4 (starved condition), which, in turn, results in increased activation of amino acid synthesis genes Since eIF2 is essential for most forms of translation initiation and therefore protein synthesis, defects in eIF2 are often lethal. (wikipedia.org)
  • mTOR
  • In 1994, Stuart L. Schreiber, David M. Sabatini and Robert T. Abraham independently discovered a protein that directly interacts with FKBP12-rapamycin, which became known as mTOR due to its homology to the yeast TOR/DRR genes. (wikipedia.org)
  • Sequence analysis of mTOR revealed it to be the direct ortholog of proteins encoded by the yeast target of rapamycin 1 and 2 (TOR1 and TOR2) genes, which Joseph Heitman, Rao Movva, and Michael N. Hall had identified in August 1991 and May 1993. (wikipedia.org)
  • The most established mTOR inhibitors are so-called rapalogs (rapamycin and its analogs), which have shown tumor responses in clinical trials against various tumor types. (wikipedia.org)
  • Many human tumors occur because of dysregulation of mTOR signaling, and can confer higher susceptibility to inhibitors of mTOR. (wikipedia.org)
  • elongation
  • 3. Other ROCK targets NHE1 (a sodium hydrogen exchanger, involved in focal adhesions and actin organisation) intermediate filament proteins: Vimentin, GFAP (glial fibrillaric acidic protein), NF-L (neurofilament L protein) F-actin binding proteins: Adducin, EF-1α (elongation factor, translation co-factor), MARCKS (myristylated alanine-rich C kinase substrate), Caponin (unknown function), and ERM (involved in linkage of the actin cytoskelton to the plasma membrane). (wikipedia.org)