• pathway
  • 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)
  • 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 abundance of cyclins is generally regulated by protein synthesis and degradation through an APC/C dependent pathway. (wikipedia.org)
  • P16/Rb pathway collaborates with the mitogenic signaling cascade for the induction of reactive oxygen species, which activates the protein kinase C delta, leading to an irreversible cell cycle arrest. (wikipedia.org)
  • inhibitory
  • This finding suggests that the ability of cyclinD-CDK complexes to sequester CIP/KIP proteins is predominates their inhibitory activity of CDK2. (wikipedia.org)
  • This flexibility could allow balanol to adapt to numerous protein microenvironments in order to exert its inhibitory properties on various protein kinases. (wikipedia.org)
  • CDK4
  • 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)
  • In doing so p27Kip1 inhibits the catalytic activity of Cdk4, which means that it prevents Cdk4 from adding phosphate residues to its principal substrate, the retinoblastoma (pRb) protein. (wikipedia.org)
  • receptor
  • The lymphocyte-specific kinase Lck is a member of the Src family of non-receptor tyrosine kinases. (ebi.ac.uk)
  • Interleukin-1 receptor associated kinase inhibitors: potential therapeutic agents for inflammatory- and immune-related disorders. (ebi.ac.uk)
  • In contrast, there was a profound and time-dependent increase in endothelial prepro-ET-1 mRNA and intravascular ET-1 abundance (by ELISA) as well as in smooth muscle endothelin B receptor mRNA and functional protein (by superfusion bioassay) on raising the perfusion pressure from 5 to 20 mm Hg, but not from 0 to 5 mm Hg, for up to 12 hours. (ahajournals.org)
  • downstream
  • Transcription of the CDKN1B gene is activated by Forkhead box class O family (FoxO) proteins which also acts downstream to promote p27 nuclear localization and decrease levels of COP9 subunit 5(COPS5) which helps in the degradation of p27. (wikipedia.org)
  • differentiation
  • SIRT2 appears to be the relevant target for cambinol-induced Daudi cell toxicity.KN-62, an inhibitor of the calmodulin-dependent protein kinases (CaMKs), enhances the terminal differentiation of retinoic acid sensitive human myeloid leukemia cell lines. (washington.edu)
  • For example, CDK6 is involved in the differentiation of T cells, acting as an inhibitor of differentiation. (wikipedia.org)
  • Regulation
  • CDK family members are highly similar to the gene products of Saccharomyces cerevisiae cdc28, and Schizosaccharomyces pombe cdc2, and are known to be important regulators of cell cycle progression in the point of regulation named R or restriction point. (wikipedia.org)
  • mutants
  • Recently, ponatinib was shown to be active against AC220-resistant kinase domain mutants of AML-expressing FLT3-ITD ( 6 , 11 ). (aacrjournals.org)
  • biochemical
  • 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)
  • human
  • Here, we examined the effect of SFK inhibitors in NCI-H2052, ACC-MESO-4 and NCI-H28 cells, mesothelioma cell lines and Met5A, a human non-malignant mesothelial cell line. (oup.com)
  • We have previously identified the compound cambinol, an inhibitor of the human sirtuins SIRT1 and SIRT2, which is selectively toxic to Burkitt's lymphoma cells. (washington.edu)
  • 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)
  • conformational
  • An aggregate analysis of many predicted structures to reduce errors in protein structure comparison caused by conformational flexibility. (ebi.ac.uk)
  • cancers
  • The role of CIP/KIP proteins in motility has also become particularly of interest in cancer where misregulation of p27 could result in increased proliferation and increased motility which may contribute to more invasive cancers. (wikipedia.org)
  • however, the exact role of CIP/KIP proteins in cancer progression has been difficult to assess because a complete loss of CIP/KIP function has not been observed in any cancers. (wikipedia.org)
  • Activation
  • Activation of tyrosine kinases by mutation of the gatekeeper threonine. (ebi.ac.uk)
  • Over the last several years, evidence has accumulated that implicates the hyperglycemia-induced activation of protein kinase C (PKC 1 ) as one of the mechanisms responsible for the development and/or progression of chronic complications of diabetes. (aspetjournals.org)