Search results for "protein kinase A"
showing 10 items of 231 documents
Induction of collagenase-3 (MMP-13) expression in human skin fibroblasts by three-dimensional collagen is mediated by p38 mitogen-activated protein k…
1999
Collagenase-3 (matrix metalloproteinase-13, MMP-13) is a recently identified human MMP with an exceptionally wide substrate specificity and restricted tissue-specific expression. Here we show that MMP-13 expression is induced in normal human skin fibroblasts cultured within three-dimensional collagen gel resulting in production and proteolytic activation of MMP-13. Induction of MMP-13 mRNAs by collagen gel was potently inhibited by blocking antibodies against alpha1 and alpha2 integrin subunits and augmented by activating antibody against beta1 integrin subunit, indicating that both alpha1 beta1 and alpha2 beta1 integrins mediate the MMP-13-inducing cellular signal generated by three-dimens…
Science Signaling Podcast: 5 August 2014
2014
This Podcast features an interview with Juliane Mooz and Krishnaraj Rajalingam, authors of a Research Article that appears in the 5 August 2014 issue of Science Signaling , about the cellular functions of the kinase ARAF. RAF proteins are serine-threonine kinases that mediate signaling through the mitogen-activated protein kinase (MAPK) pathway, and aberrant RAF activity can transform normal cells into cancerous cells. There are three RAFs in mammals: ARAF, BRAF, and CRAF. The most studied of these is BRAF, mutations in which are associated with various cancers. Whereas the cellular functions of BRAF and CRAF have been extensively studied, not much is known about ARAF. Mooz et al . found th…
Identification and characterization of an ABA-activated MAP kinase cascade in Arabidopsis thaliana.
2015
†These authors contributed equally to the work. Accession numbers Sequence data from this article can be found in Arabidopsis Genome Initiative or GenBank/EMBL databases under the following accession numbers: At1g10210 (MPK1), At1g59580 (MPK2), At2g43790 (MPK6), At2g18170 (MPK7), At1g18150 (MPK8), At4g36450 (MPK14), At5g40440 (MKK3), At2g32510 (MAP3K17) and At1g05100 (MAP3K18). SUMMARY Abscisic acid (ABA) is a major phytohormone involved in important stress-related and developmental plant processes. Recent phosphoproteomic analyses revealed a large set of ABA-triggered phosphoproteins as putative mitogen-activated protein kinase (MAPK) targets, although the evidence for MAPKs involved in AB…
Synthesis and biological evaluation of cycloalkylidene carboxylic acids as novel effectors of Ras/Raf interaction.
2002
The protooncogenes Ras and Raf play important roles in signal transduction pathways regulated by mitogen-activated protein kinases. Mutations of Ras that arrest the protein in its active state are frequently implicated in tumor formation. We used Ras and Raf proteins in the yeast two-hybrid system to search for natural or synthesized substances capable of modulating Ras/Raf interaction by specifically binding to one of the interacting partners. We found that cycloalkylidene carboxylic acids enhanced Ras/Raf interaction by acting on the cysteine-rich domain of Raf. Several analogues of the active substance 2-cyclohexylidene propanoic acid were synthesized and the importance of the semicyclic…
The activation of ERK1/2 MAP kinases in glioblastoma pathobiology and its relationship with EGFR amplification.
2008
The ERK1/2 activated protein kinase (MAPK) pathway is a critical signaling system that mediates ligand-stimulated signals for the induction of cell proliferation, differentiation and survival, involved in malignant transformation. The purpose of this study was to determine the activation of ERK1/2 in this tumor, and to determine the relationship of ERK1/2 activation with the amplification/overexpression of EGFR as well as with 9p21 locus gene alterations, both of which are genetic factors frequently associated with glioblastoma. We used immunohistochemistry and Western blot analysis to analyze the activation of ERK1/2 in 22 patients with glioblastoma, and we studied the amplification/overex…
The Late Endosomal Adaptor Molecule p14 (LAMTOR2) Regulates TGFβ1-Mediated Homeostasis of Langerhans Cells
2014
Langerhans cells (LCs), a sub-population of dendritic cells (DCs) in the skin, participate in the regulation of immunity and peripheral tolerance. The adaptor molecule p14 is part of the late endosomal/lysosomal adaptor and mitogen-activated protein kinase and mammalian target of rapamycin (mTOR) activator/regulator (LAMTOR) complex, which mediates the activation of lysosome-associated extracellular signaling regulated kinase (ERK) and the mTOR cascade. In previous work, we demonstrated that CD11c-specific deficiency of p14 disrupts LC homeostasis by affecting the LAMTOR-mediated ERK and mTOR signaling. In this study, we extended our analysis on p14 deficiency specifically in LCs. Langerin-…
Effect of simultaneous inhibition of TNF-α production and xanthine oxidase in experimental acute pancreatitis: The role of mitogen activated protein …
2004
Javier Pereda et al.
2-(6-Methoxy-7H-purin-7-yl)-1-phenylethanone monohydrate
2007
The crystal structure of the title compound, C14H12N4O2·H2O, was determined in the course of our studies of the synthesis and optimization of 7-aryl-7H-purines as inhibitors of the vascular endothelial growth factor receptor (VEGF-R), c-Jun NH2-terminal protein kinase 3 (JNK3) and the p38α mitogen-activated protein kinase (MAPK). In the title compound, two molecules are associated with each other through O—H⋯N hydrogen bonds to different N atoms in the purine ring system. The compound was prepared via a regioselective synthesis using the methyl(aqua)cobaloxime complex, CH3Co(DH)2OH2, as a temporary auxiliary. The X-ray crystallographic results confirmed the regioselective N-7 alkylation …
Dimerization of the kinase ARAF promotes MAPK pathway activation and cell migration.
2014
The RAF family of kinases mediates RAS signaling, and RAF inhibitors can be effective for treating tumors with BRAF V600E mutant protein. However, RAF inhibitors paradoxically accelerate metastasis in RAS -mutant tumors and become ineffective in BRAF V600E tumors because of reactivation of downstream mitogen-activated protein kinase (MAPK) signaling. We found that the RAF isoform ARAF has an obligatory role in promoting MAPK activity and cell migration in a cell type–dependent manner. Knocking down ARAF prevented the activation of MAPK kinase 1 (MEK1) and extracellular signal–regulated kinase 1 and 2 (ERK1/2) and decreased the number of protrusions from tumor cell spheroids in three-dimensi…
Structural Optimization of a Pyridinylimidazole Scaffold: Shifting the Selectivity from p38α Mitogen-Activated Protein Kinase to c-Jun N-Terminal Kin…
2018
Starting from known p38α mitogen-activated protein kinase (MAPK) inhibitors, a series of inhibitors of the c-Jun N-terminal kinase (JNK) 3 was obtained. Altering the substitution pattern of the pyridinylimidazole scaffold proved to be effective in shifting the inhibitory activity from the original target p38α MAPK to the closely related JNK3. In particular, a significant improvement for JNK3 selectivity could be achieved by addressing the hydrophobic region I with a small methyl group. Furthermore, additional structural modifications permitted to explore structure–activity relationships. The most potent inhibitor 4-(4-methyl-2-(methylthio)-1H-imidazol-5-yl)-N-(4-morpholinophenyl)pyridin-2-a…