Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.24 (mitogen-activated protein kinase)
 95,810 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Protein kinase C (PKC), p38 MAP kinase, and mitogen-activated protein kinase-activated kinases 2 and 3 (MAPKAPK2 and MAPKAPK3) have been implicated in ischemic preconditioning (PC) of the heart to reduce damage following a myocardial infarct. This study examined whether extracellular signal-regulated kinase (Erk) 1, p70 ribosomal S6 kinase (p70 S6K), casein kinase 2 (CK2), and other hsp27 kinases are also activated by PC, and if they are required for protection in rabbit hearts. CK2 and hsp27 kinase activities declined during global ischemia in control hearts, whereas PC with 5 min ischemia and 10 min reperfusion increased their activities during global ischemia. Resource Q chromatography resolved two distinct peaks of hsp27 phosphotransferase activities; the first peak (at 0.36 M NaCl) appeared to correspond to the 55-kDa MAPKAPK2. Erk1 activity was elevated in both control and PC hearts after post-ischemic reperfusion, but no change was observed in p70 S6K activity. Infarct size (measured by triphenyltetrazolium staining) in isolated rabbit hearts subjected to 30 min regional ischemia and 2 h reperfusion was 31.0+/-2.6% of the risk zone in controls and was 10.3+/-2.2% in PC hearts (p<0.001). Neither the CK2 inhibitor 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB) nor the Mek1/2 inhibitor PD98059 infused during ischemia blocked protection by PC. The activation of CK2 and Erk1 in ischemic preconditioned hearts appear to be epiphenomena and not required for the reduction of infarction from myocardial ischemia.
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PMID:Ischemia induced activation of heat shock protein 27 kinases and casein kinase 2 in the preconditioned rabbit heart. 1066 33

Using a combination of targeted differential display for induced protein kinases and differential library screening, we identified mitogen-activated protein kinase activated protein kinase 2 (MAPKAPK2), as a primary response gene whose transcription is stimulated by membrane depolarization and by forskolin in rat PC12 pheochromocytoma cells. MAPKAPK3 was neither induced nor repressed by similar treatments. The increase in MAPKAPK2 mRNA is preceded by an increase in a MAPKAPK2 intron-containing RNA precursor, indicating that the increase in message is due at least in part to increased transcription. The open reading frame of full-length rat MAPKAPK2 cDNA is 99% identical to mouse MAPKAPK2 and 92% identical to human MAPKAPK2. The human MAPKAPK2 predicted protein contains 14 additional amino acids in the proline-rich N-terminal domain, when compared to murine and rat MAPKAPK2 predicted proteins. The MAPKAPK2 form found in PC12 cells corresponds to variant 2 in the human; this ortholog carries a nuclear translocation signal near its C-terminus. MAPKAPK2 message is also induced in the dentate gyrus, CA1, and CA3 of the rat hippocampus between 2-4 hr after the onset of kainic acid-induced seizures.
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PMID:MAPKAP kinase-2 is a primary response gene induced by depolarization in PC12 cells and in brain. 1538 39

Autophagy is a fundamental adaptive response to amino acid starvation orchestrated by conserved gene products, the autophagy (ATG) proteins. However, the cellular cues that activate the function of ATG proteins during amino acid starvation are incompletely understood. Here we show that two related stress-responsive kinases, members of the p38 mitogen-activated protein kinase (MAPK) signaling pathway MAPKAPK2 (MK2) and MAPKAPK3 (MK3), positively regulate starvation-induced autophagy by phosphorylating an essential ATG protein, Beclin 1, at serine 90, and that this phosphorylation site is essential for the tumor suppressor function of Beclin 1. Moreover, MK2/MK3-dependent Beclin 1 phosphorylation (and starvation-induced autophagy) is blocked in vitro and in vivo by BCL2, a negative regulator of Beclin 1. Together, these findings reveal MK2/MK3 as crucial stress-responsive kinases that promote autophagy through Beclin 1 S90 phosphorylation, and identify the blockade of MK2/3-dependent Beclin 1 S90 phosphorylation as a mechanism by which BCL2 inhibits the autophagy function of Beclin 1.
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PMID:The stress-responsive kinases MAPKAPK2/MAPKAPK3 activate starvation-induced autophagy through Beclin 1 phosphorylation. 2699 42