• 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)
  • 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)
  • 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)
  • receptors
  • Soluble DPP-4 up-regulates toll-like receptors and augments inflammatory reactions, which are ameliorated by vildagliptin or mannose-6-phosphate. (gopubmed.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)
  • mammalian
  • 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)
  • 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)
  • 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)
  • Thus in both cases, ROCK activation by Rho induces the formation of actin stress fibers, actin filament bundles of opposing polarity, containing myosin II, tropomyosin, caldesmon and MLC-kinase, and consequently of focal contacts, which are immature integrin-based adhesion points with the extracellular substrate. (wikipedia.org)
  • 1994
  • 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)
  • 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)
  • Regulation
  • RKIP is a member of the phosphatidylethanolamine-binding protein family and has displayed disruptive regulation on the Raf-1-MEK1/2, ERK1/2 and NF-kappaB signalling pathways, by interaction with the Raf-1 kinase. (wikipedia.org)
  • The up-regulation of annexin-V-binding following zosuquidar (4 µg/ml) treatment was significantly blunted by removal of extracellular Ca2+, by presence of p38 kinase inhibitor SB203580 (2 µM) and by presence of protein kinase C inhibitor calphostin (100 nM). (gopubmed.org)
  • 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)
  • 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)
  • mechanism
  • As a probable mechanism, we found that sDPP-4 caused dose-dependent increases in the expression levels of toll-like receptor 4 (TLR4) and TLR2 in RAW264.7 cells, and that these alterations were inhibited by vildagliptin, M6P, or bisindolylmaleimide II, a protein kinase C inhibitor. (gopubmed.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)
  • The discovery of mTOR was made a few decades ago while investigating the mechanism of action of its inhibitor, rapamycin. (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)
  • activity
  • These NF1 cells also demonstrated increased constitutive activity of the extracellular signal-regulated kinases 1 and 2 (ERK1,2) mitogen-activated protein (MAP) kinases compared with a sporadic malignant schwannoma cell line that maintains neurofibromin expression (STS-26T). (aspetjournals.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)
  • 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)
  • ROCKs regulate cell-cell adhesion: Loss of ROCK activity seems to lead to loss of tight junction integrity in endothelial cells. (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)
  • mTOR
  • 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)
  • It appears that growth factors, amino acids, ATP, and oxygen levels regulate mTOR signaling. (wikipedia.org)
  • Many human tumors occur because of dysregulation of mTOR signaling, and can confer higher susceptibility to inhibitors of mTOR. (wikipedia.org)
  • highly conserved
  • This highly conserved protein family is found in both plants and mammals, and this protein is 99% identical to the mouse and rat orthologs. (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)
  • The protein is highly conserved among evolutionary remote species - indicating a large impact of mutations on cell viability. (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)
  • subcellular localization
  • Many animal and human studies have described alterations in the abundance or subcellular localization of connexin proteins under a variety of pathological conditions, including hypertrophy, heart failure, ischemic heart diseases, and atrial fibrillation ( 1,2 ). (onlinejacc.org)
  • Sequence
  • 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)
  • The encoded protein lacks the protein destabilizing (PEST) sequence that is present in other family members. (wikipedia.org)