Identification of a Novel Inhibitor of Mitogen-activated Protein Kinase Kinase*
Journal of Biological Chemistry, 1998 The compound U0126 (1,4-diamino-2,3-dicyano-1,4-bis[2-aminophenylthio]butadiene) was identified as an inhibitor of AP-1 transactivation in a cell-based reporter assay. U0126 was also shown to inhibit endogenous promoters containing AP-1 response elements
M. Favata +13 more
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Discovery of catalytically active orthologues of the Parkinson's disease kinase PINK1: analysis of substrate specificity and impact of mutations [PDF]
Open Biology, 2011 Missense mutations of the phosphatase and tensin homolog (PTEN)-induced kinase 1 (PINK1) gene cause autosomal-recessive Parkinson's disease. To date, little is known about the intrinsic catalytic properties of PINK1 since the human enzyme displays such ...
Helen I. Woodroof +9 more
doaj +1 more source
Journal of Biological Chemistry, 1995 PD 098059 has been shown previously to inhibit the dephosphorylated form of mitogen-activated protein kinase kinase-1 (MAPKK1) and a mutant MAPKK1(S217E,S221E), which has low levels of constitutive activity (Dudley, D. T., Pang, L., Decker, S.
D. Alessi +4 more
semanticscholar +1 more source
Coordinate Regulation of IκB Kinases by Mitogen-Activated Protein Kinase Kinase Kinase 1 and NF-κB-Inducing Kinase [PDF]
Molecular and Cellular Biology, 1998 IkappaB kinases (IKKalpha and IKKbeta) are key components of the IKK complex that mediates activation of the transcription factor NF-kappaB in response to extracellular stimuli such as inflammatory cytokines, viral and bacterial infection, and UV irradiation.
Anning Lin +2 more
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Protein Kinase Mitogen-activated Protein Kinase Kinase Kinase Kinase 4 (MAP4K4) Promotes Obesity-induced Hyperinsulinemia [PDF]
Journal of Biological Chemistry, 2016 Previous studies revealed a paradox whereby mitogen-activated protein kinase kinase kinase kinase 4 (Map4k4) acted as a negative regulator of insulin sensitivity in chronically obese mice, yet systemic deletion of Map4k4 did not improve glucose tolerance.
Roth Flach, Rachel J. +12 more
openaire +4 more sources
Prediction of kinase inhibitor response using activity profiling, in-vitro screening, and elastic net regression [PDF]
BMC Systems Biology 2014, 8:74, 2013 Many kinase inhibitors have been approved as cancer therapies. Recently, libraries of kinase inhibitors have been extensively profiled, thus providing a map of the strength of action of each compound on a large number of its targets. These profiled libraries define drug-kinase networks that can predict the effectiveness of new untested drugs and ...
arxiv +1 more source
New England Journal of Medicine, 2001 BACKGROUND BCR-ABL is a constitutively activated tyrosine kinase that causes chronic myeloid leukemia (CML). Since tyrosine kinase activity is essential to the transforming function of BCR-ABL, an inhibitor of the kinase could be an effective treatment ...
B. Druker +10 more
semanticscholar +1 more source
Regulation of signal duration and the statistical dynamics of kinase activation by scaffold proteins [PDF]
PLoS Comput Biol. 2008 Jun 27;4(6):e1000099, 2008 Scaffolding proteins that direct the assembly of multiple kinases into a spatially localized signaling complex are often essential for the maintenance of an appropriate biological response. Although scaffolds are widely believed to have dramatic effects on the dynamics of signal propagation, the mechanisms that underlie these consequences are not well ...
arxiv +1 more source
Pharmacological LRRK2 kinase inhibition induces LRRK2 protein destabilization and proteasomal degradation [PDF]
, 2016 Leucine-rich repeat kinase 2 (LRRK2) kinase activity is increased in several pathogenic mutations, including the most common mutation, G2019S, and is known to play a role in Parkinson’s disease (PD) pathobiology.
Baekelandt, V. +5 more
core +1 more source
Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer.
New England Journal of Medicine, 2010 BACKGROUND Oncogenic fusion genes consisting of EML4 and anaplastic lymphoma kinase (ALK) are present in a subgroup of non-small-cell lung cancers, representing 2 to 7% of such tumors. We explored the therapeutic efficacy of inhibiting ALK in such tumors
E. Kwak +33 more
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