Targeting the Raf-MEK-ERK mitogen-activated protein kinase cascade for the treatment of cancer

Oncogene, Journal Year: 2007, Volume and Issue: 26(22), P. 3291 - 3310

Published: May 14, 2007

Language: Английский

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The selectivity of protein kinase inhibitors: a further update

Biochemical Journal, Journal Year: 2007, Volume and Issue: 408(3), P. 297 - 315

Published: Nov. 28, 2007

The specificities of 65 compounds reported to be relatively specific inhibitors protein kinases have been profiled against a panel 70–80 kinases. On the basis this information, effects that we studied in cells and other data literature, recommend use following small-molecule inhibitors: SB 203580/SB202190 BIRB 0796 used parallel assess physiological roles p38 MAPK (mitogen-activated kinase) isoforms, PI-103 wortmannin inhibit phosphatidylinositol (phosphoinositide) 3-kinases, PP1 or PP2 with Src-I1 (Src inhibitor-1) Src family members; PD 184352 0325901 MKK1 (MAPK kinase-1) plus MKK5, Akt-I-1/2 activation PKB (protein kinase B/Akt), rapamycin TORC1 [mTOR (mammalian target rapamycin)–raptor (regulatory associated mTOR) complex], CT 99021 GSK3 (glycogen synthase 3), BI-D1870 SL0101 FMK (fluoromethylketone) RSK (ribosomal S6 kinase), D4476 CK1 (casein 1), VX680 Aurora kinases, roscovitine as pan-CDK (cyclin-dependent inhibitor. We also identified harmine potent inhibitor DYRK1A (dual-specificity tyrosine-phosphorylated -regulated 1A) vitro. results further emphasized need for considerable caution using these enzymes. Despite being widely, many analysed were too non-specific useful conclusions made, than exclude involvement particular cellular processes.

Language: Английский

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A quantitative analysis of kinase inhibitor selectivity

Nature Biotechnology, Journal Year: 2008, Volume and Issue: 26(1), P. 127 - 132

Published: Jan. 1, 2008

Language: Английский

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Comprehensive analysis of kinase inhibitor selectivity

Nature Biotechnology, Journal Year: 2011, Volume and Issue: 29(11), P. 1046 - 1051

Published: Oct. 30, 2011

Language: Английский

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A small molecule–kinase interaction map for clinical kinase inhibitors

Nature Biotechnology, Journal Year: 2005, Volume and Issue: 23(3), P. 329 - 336

Published: Feb. 13, 2005

Language: Английский

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Calmodulin-dependent protein kinase kinase-β is an alternative upstream kinase for AMP-activated protein kinase

Cell Metabolism, Journal Year: 2005, Volume and Issue: 2(1), P. 9 - 19

Published: July 1, 2005

Language: Английский

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MAPK cascade signalling and synaptic plasticity

Nature reviews. Neuroscience, Journal Year: 2004, Volume and Issue: 5(3), P. 173 - 183

Published: Feb. 20, 2004

Language: Английский

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Physiology of Cell Volume Regulation in Vertebrates

Physiological Reviews, Journal Year: 2009, Volume and Issue: 89(1), P. 193 - 277

Published: Jan. 1, 2009

The ability to control cell volume is pivotal for function. Cell perturbation elicits a wide array of signaling events, leading protective (e.g., cytoskeletal rearrangement) and adaptive altered expression osmolyte transporters heat shock proteins) measures and, in most cases, activation regulatory transport. After acute swelling, regulated by the process decrease (RVD), which involves KCl cotransport channels mediating K + , Cl − taurine efflux. Conversely, after shrinkage, increase (RVI), mediated primarily Na /H exchange, -K -2Cl cotransport, channels. Here, we review detail current knowledge regarding molecular identity these transport pathways their regulation by, e.g., membrane deformation, ionic strength, Ca 2+ protein kinases phosphatases, elements, GTP binding proteins, lipid mediators, reactive oxygen species, upon changes volume. We also discuss nature upstream elements sensing vertebrate organisms. Importantly, impacts on physiological processes, including transepithelial transport; migration, proliferation, death; function as specific signals regulating processes. A discussion this issue concludes review.

Language: Английский

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Mammalian MAPK Signal Transduction Pathways Activated by Stress and Inflammation: A 10-Year Update

Physiological Reviews, Journal Year: 2012, Volume and Issue: 92(2), P. 689 - 737

Published: April 1, 2012

The mammalian stress-activated families of mitogen-activated protein kinases (MAPKs) were first elucidated in 1994, and by 2001, substantial progress had been made identifying the architecture pathways upstream these as well cataloguing candidate substrates. This information remains largely sound. Nevertheless, an informed understanding physiological pathophysiological roles remained to be accomplished. In past decade, there has explosion new work using RNAi cells, transgenic, knockout conditional technology mice that provided valuable insight into functions MAPK pathways. These findings have important implications our organ development, innate acquired immunity, diseases such atherosclerosis, tumorigenesis, type 2 diabetes. developments bring us within striking distance development validation novel treatment strategies. Herein we summarize molecular components stress-regulated their regulation described thus far. We then review some vivo

Language: Английский

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Specific inhibition of cyclin-dependent kinase 4/6 by PD 0332991 and associated antitumor activity in human tumor xenografts

Molecular Cancer Therapeutics, Journal Year: 2004, Volume and Issue: 3(11), P. 1427 - 1438

Published: Nov. 1, 2004

Abstract PD 0332991 is a highly specific inhibitor of cyclin-dependent kinase 4 (Cdk4) (IC50, 0.011 μmol/L) and Cdk6 0.016 μmol/L), having no activity against panel 36 additional protein kinases. It potent antiproliferative agent retinoblastoma (Rb)-positive tumor cells in vitro, inducing an exclusive G1 arrest, with concomitant reduction phospho-Ser780/Ser795 on the Rb protein. Oral administration to mice bearing Colo-205 human colon carcinoma produces marked regression. Therapeutic doses cause elimination phospho-Rb proliferative marker Ki-67 tissue down-regulation genes under transcriptional control E2F. The results indicate that inhibition Cdk4/6 alone sufficient regression net burden some tumors.

Language: Английский

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