• 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 pathway involving the cyclic guanosine-3′,5′-monophosphate (cGMP) may provide a unique signaling mechanism in regulating axon branching. (jneurosci.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)
  • AZD6244 ( ARRY-142886 ) is an investigational anticancer drug that is designed to block a critical component (MEK (methyl ethyl ketone)) of a pathway (MAP (mitogen-activated protein) kinase pathway) that causes some lung cancer cells to grow. (clinicaltrials.gov)
  • 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)
  • 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)
  • amino
  • The gene spans 231,706 base pairs and encodes a 326 amino acid protein with a kinase function. (wikipedia.org)
  • 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)
  • 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)
  • mammalian
  • 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)
  • 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)
  • These two complexes have a separate network of protein partners, feedback loops, substrates, and regulators. (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)
  • 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)
  • 1. ROCK is a key regulator of actin organization and thus a regulator of cell migration as follows: Different substrates can be phosphorylated by ROCKs, including LIM kinase, myosin light chain (MLC) and MLC phosphatase. (wikipedia.org)
  • induce
  • 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)
  • receptors
  • Chemokines are classified into CXC, CC, C, and CX3C families, which bind to and activate members of a superfamily of 7-transmembrane domain, G protein-coupled receptors differentially expressed and regulated in leukocytes ( 2 ). (jimmunol.org)
  • 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)
  • caspase
  • 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)
  • 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)
  • 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)
  • Screening and Chemical Studies of New Cell Functions-regulating Natural Products. (nii.ac.jp)
  • 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)
  • 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)
  • 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)
  • 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)
  • GCN2 also regulates the cell cycle by delaying entry into S phase upon ultraviolet (UV) radiation and exposure to methyl methanesulfonate (MMS). (wikipedia.org)
  • Potent
  • As it is a potent inhibitor of angiogenesis, it also strongly suppresses tumor growth. (sigmaaldrich.com)
  • To improve arterial sclerosis that was caused by estrification of liberated cholesterol from denatured lipoprotein in bloods, potent inhibitors of cholesterol esterase were searched in microbial products, … More and ikarugamycin and other three acive compounds isolated, their structures elucidated, and their mode of action investigated. (nii.ac.jp)
  • mechanism
  • The discovery of mTOR was made a few decades ago while investigating the mechanism of action of its inhibitor, rapamycin. (wikipedia.org)
  • 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)
  • 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)
  • activity
  • 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)
  • 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)
  • 2. Other functions and targets RhoA-GTP stimulates the phospholipid phosphatase activity of PTEN (phosphatase and tensin homologue), a human tumor suppressor protein. (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)
  • genes
  • The Nia1nit2 mutant with defects in genes encoding the nitrate reductase and regulatory protein NIT2 respectively was found to exhibit normal chemotaxis to nitrite. (mdpi.com)
  • Antiangiogenic agent, down-regulates the transcription of genes involved in controlling angiogenesis. (sigmaaldrich.com)
  • SREBP-1c actions upon genes regulating fatty-acid and triglyceride synthesis and is reduced by leucine deprivation in the liver in a GCN2-dependant manner. (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)
  • motif
  • Moreover, the sequence of the protein comprises a zinc finger motif that was shown to play a role in both ternary complex and 43S preinitiation complex formation. (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)
  • The crucial contribution to GCN2 function is the promotion of tRNA binding and the stimulation of the kinase domain via physical interaction. (wikipedia.org)