MAP-kinase-activated protein kinase 2 expression and activity is induced after neuronal depolarization.
Mitogen-activated protein kinase-activated protein kinase (MK)2 is one of several downstream targets of p38 mitogen-activated protein kinase and has a well documented role in inflammation. Here, we describe a possible new function of MK2. We show that triggering depolarization by potassium chloride or increasing the cellular cAMP by forskolin treatment led to elevated levels of expression and activity of mouse MK2. In both treatments, the kinase inhibitor H89 completely prevented the up-regulation of MK2 at the transcript level. By the use of different cell lines we demonstrated that the induction of MK2 expression is characteristic of neuronal cells and is absent in fibroblasts, macrophages and kidney cells. In vivo, induction of a status epilepticus by systemic administration of the chemoconvulsant kainic acid resulted in markedly reduced neurodegeneration in the pyramidal layer of the hippocampus, dentate gyrus and hilus of MK2-deficient mice compared with wild-type mice. Together, our data suggest a possible role of MK2 in the cellular response after neuronal depolarization, in particular in excitotoxicity.
Thomas
Tobias
T
Institute of Biochemistry, Hannover Medical School, Carl-Neuberg-Strasse 1, D-30625 Hannover, Germany.
Hitti
Edward
E
Kotlyarov
Alexey
A
Potschka
Heidrun
H
Gaestel
Matthias
M
D000818:Animals; D002478:Cells, Cultured; D005576:Colforsin / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D004789:Enzyme Activation; D004795:Enzyme Stability; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D007546:Isoquinolines / Q000378:metabolism; D007608:Kainic Acid / Q000494:pharmacology; D008564:Membrane Potentials / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D016716:PC12 Cells; D011189:Potassium Chloride / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D012640:Seizures / Q000139:chemically induced; D015398:Signal Transduction / Q000502:physiology; D013449:Sulfonamides / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D000099190:MAP-Kinase-Activated Kinase 2
D005576:Colforsin; D017868:Cyclic AMP-Dependent Protein Kinases; D018690:Excitatory Amino Acid Agonists; D047908:Intracellular Signaling Peptides and Proteins; D007546:Isoquinolines; D007608:Kainic Acid; D011189:Potassium Chloride; D047428:Protein Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger; D013449:Sulfonamides; D048051:p38 Mitogen-Activated Protein Kinases; D000099190:MAP-Kinase-Activated Kinase 2; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide