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Mitogen-activated protein kinase phosphatases inactivate stress-activated protein kinase pathways in vivo. 1997

D D Hirsch, and P J Stork
Vollum Institute, Oregon Health Sciences University, Portland, Oregon 97201, USA.

The c-Jun N-terminal protein kinases (JNKs), also called stress-activated protein kinases, are members of the growing family of serine/threonine kinases in the mitogen-activated protein (MAP) kinase superfamily. Like other MAP kinases, JNKs are activated via phosphorylation on adjacent threonine and tyrosine residues and can be inactivated by a unique family of dual specificity phosphatases, called MAP kinase phosphatases (MKPs). MKPs are encoded by immediate early genes and induced in response to environmental stressors and growth factor stimulation. Two prevalent isoforms of MKP, MKP1 and MKP2, are co-expressed in a wide variety of cell types. In this study, we examined the actions of MKP1 and MKP2 on JNK1 and JNK2. JNK1 phosphorylation and activation was inhibited by expression of both MKP1 and MKP2, although MKP1 selectivity toward JNK1 appeared significantly higher than that of MKP2. In contrast, JNK2 activity was inhibited by either phosphatase to similar degrees. Both MKP1 and MKP2 were highly effective at blocking the activation of the physiological target of JNK activation, the transcription factor c-Jun. In PC12 cells, MKP1 and MKP2 are transcriptionally induced following stimulation by nerve growth factor. In these cells, UV light-evoked JNK activation was reduced by pretreatment with nerve growth factor. Therefore, JNKs may be selective targets of MKP action in certain cells.

UI MeSH Term Description Entries
D008934 Mitogens Substances that stimulate mitosis and lymphocyte transformation. They include not only substances associated with LECTINS, but also substances from streptococci (associated with streptolysin S) and from strains of alpha-toxin-producing staphylococci. (Stedman, 25th ed) Mitogen,Phytomitogen,Phytomitogens
D009414 Nerve Growth Factors Factors which enhance the growth potentialities of sensory and sympathetic nerve cells. Neurite Outgrowth Factor,Neurite Outgrowth Factors,Neuronal Growth-Associated Protein,Neuronotrophic Factor,Neurotrophic Factor,Neurotrophic Factors,Neurotrophin,Neurotrophins,Growth-Associated Proteins, Neuronal,Neuronal Growth-Associated Proteins,Neuronotrophic Factors,Neurotrophic Protein,Neurotrophic Proteins,Proteins, Neuronal Growth-Associated,Factor, Neurite Outgrowth,Factor, Neuronotrophic,Factor, Neurotrophic,Factors, Nerve Growth,Factors, Neurite Outgrowth,Factors, Neuronotrophic,Factors, Neurotrophic,Growth Associated Proteins, Neuronal,Growth-Associated Protein, Neuronal,Neuronal Growth Associated Protein,Neuronal Growth Associated Proteins,Outgrowth Factor, Neurite,Outgrowth Factors, Neurite,Protein, Neuronal Growth-Associated
D010749 Phosphoprotein Phosphatases A group of enzymes removing the SERINE- or THREONINE-bound phosphate groups from a wide range of phosphoproteins, including a number of enzymes which have been phosphorylated under the action of a kinase. (Enzyme Nomenclature, 1992) Phosphoprotein Phosphatase,Phosphoprotein Phosphohydrolase,Protein Phosphatase,Protein Phosphatases,Casein Phosphatase,Ecto-Phosphoprotein Phosphatase,Nuclear Protein Phosphatase,Phosphohistone Phosphatase,Phosphoprotein Phosphatase-2C,Phosphoseryl-Protein Phosphatase,Protein Phosphatase C,Protein Phosphatase C-I,Protein Phosphatase C-II,Protein Phosphatase H-II,Protein-Serine-Threonine Phosphatase,Protein-Threonine Phosphatase,Serine-Threonine Phosphatase,Threonine Phosphatase,Ecto Phosphoprotein Phosphatase,Phosphatase C, Protein,Phosphatase C-I, Protein,Phosphatase C-II, Protein,Phosphatase H-II, Protein,Phosphatase, Casein,Phosphatase, Ecto-Phosphoprotein,Phosphatase, Nuclear Protein,Phosphatase, Phosphohistone,Phosphatase, Phosphoprotein,Phosphatase, Phosphoseryl-Protein,Phosphatase, Protein,Phosphatase, Protein-Serine-Threonine,Phosphatase, Protein-Threonine,Phosphatase, Serine-Threonine,Phosphatase, Threonine,Phosphatase-2C, Phosphoprotein,Phosphatases, Phosphoprotein,Phosphatases, Protein,Phosphohydrolase, Phosphoprotein,Phosphoprotein Phosphatase 2C,Phosphoseryl Protein Phosphatase,Protein Phosphatase C I,Protein Phosphatase C II,Protein Phosphatase H II,Protein Phosphatase, Nuclear,Protein Serine Threonine Phosphatase,Protein Threonine Phosphatase,Serine Threonine Phosphatase
D010957 Plasmids Extrachromosomal, usually CIRCULAR DNA molecules that are self-replicating and transferable from one organism to another. They are found in a variety of bacterial, archaeal, fungal, algal, and plant species. They are used in GENETIC ENGINEERING as CLONING VECTORS. Episomes,Episome,Plasmid
D004789 Enzyme Activation Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme. Activation, Enzyme,Activations, Enzyme,Enzyme Activations
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D014162 Transfection The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES. Transfections
D014466 Ultraviolet Rays That portion of the electromagnetic spectrum immediately below the visible range and extending into the x-ray frequencies. The longer wavelengths (near-UV or biotic or vital rays) are necessary for the endogenous synthesis of vitamin D and are also called antirachitic rays; the shorter, ionizing wavelengths (far-UV or abiotic or extravital rays) are viricidal, bactericidal, mutagenic, and carcinogenic and are used as disinfectants. Actinic Rays,Black Light, Ultraviolet,UV Light,UV Radiation,Ultra-Violet Rays,Ultraviolet Light,Ultraviolet Radiation,Actinic Ray,Light, UV,Light, Ultraviolet,Radiation, UV,Radiation, Ultraviolet,Ray, Actinic,Ray, Ultra-Violet,Ray, Ultraviolet,Ultra Violet Rays,Ultra-Violet Ray,Ultraviolet Black Light,Ultraviolet Black Lights,Ultraviolet Radiations,Ultraviolet Ray
D015971 Gene Expression Regulation, Enzymologic Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis. Enzymologic Gene Expression Regulation,Regulation of Gene Expression, Enzymologic,Regulation, Gene Expression, Enzymologic
D048031 JNK Mitogen-Activated Protein Kinases A subgroup of mitogen-activated protein kinases that activate TRANSCRIPTION FACTOR AP-1 via the phosphorylation of C-JUN PROTEINS. They are components of intracellular signaling pathways that regulate CELL PROLIFERATION; APOPTOSIS; and CELL DIFFERENTIATION. jun N-Terminal Kinase,c-jun Amino-Terminal Kinase,c-jun N-Terminal Kinase,jun-NH2-Terminal Kinase,jun-NH2-Terminal Kinases,Amino-Terminal Kinase, c-jun,JNK Mitogen Activated Protein Kinases,Kinase, jun N-Terminal,N-Terminal Kinase, c-jun,N-Terminal Kinase, jun,c jun Amino Terminal Kinase,c jun N Terminal Kinase,jun N Terminal Kinase,jun NH2 Terminal Kinase,jun NH2 Terminal Kinases

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