Document Detail


Elimination of protein kinase MK5/PRAK activity by targeted homologous recombination.
MedLine Citation:
PMID:  14560018     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
MK5 (mitogen-activated protein kinase [MAPK]-activated protein kinase 5), also designated PRAK (p38-regulated and -activated kinase), was deleted from mice by homologous recombination. Although no MK5 full-length protein and kinase activity was detected in the MK5 knockout mice, the animals were viable and fertile and did not display abnormalities in tissue morphology or behavior. In addition, these mice did not show increased resistance to endotoxic shock or decreased lipopolysaccharide-induced cytokine production. Hence, MK5 deletion resulted in a phenotype very different from the complex inflammation-impaired phenotype of mice deficient in MK2, although MK2 and MK5 exhibit evolutional, structural, and apparent extensive functional similarities. To explain this discrepancy, we used wild-type cells and embryonic fibroblasts from both MK2 and MK5 knockout mice as controls to reexamine the mechanism of activation, the interaction with endogenous p38 MAPK, and the substrate specificity of both enzymes. In contrast to MK2, which shows interaction with and chaperoning properties for p38 MAPK and which is activated by extracellular stresses such as arsenite or sorbitol treatment, endogenous MK5 did not show these properties. Furthermore, endogenous MK5 is not able to phosphorylate Hsp27 in vitro and in vivo. We conclude that the differences between the phenotypes of MK5- and MK2-deficient mice result from clearly different functional properties of both enzymes.
Authors:
Yu Shi; Alexey Kotlyarov; Kathrin Laabeta; Achim D Gruber; Elke Butt; Katrin Marcus; Helmut E Meyer; Anke Friedrich; Hans-Dieter Volk; Matthias Gaestel
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Molecular and cellular biology     Volume:  23     ISSN:  0270-7306     ISO Abbreviation:  Mol. Cell. Biol.     Publication Date:  2003 Nov 
Date Detail:
Created Date:  2003-10-15     Completed Date:  2003-12-04     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  8109087     Medline TA:  Mol Cell Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  7732-41     Citation Subset:  IM    
Affiliation:
Institute of Biochemistry, Medical School Hannover, 30625 Hannover, Germany.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cells, Cultured
Cytokines / immunology,  metabolism
Heat-Shock Proteins*
Intracellular Signaling Peptides and Proteins
Lipopolysaccharides / metabolism
Mice
Mice, Knockout
Mitogen-Activated Protein Kinases / genetics,  metabolism
Muscle, Skeletal / cytology,  metabolism
Myocardium / cytology,  metabolism
Neoplasm Proteins / metabolism
Pancreas / cytology,  metabolism
Phenotype
Protein Binding
Protein Kinases*
Protein-Serine-Threonine Kinases / genetics,  metabolism*
Recombination, Genetic*
p38 Mitogen-Activated Protein Kinases
Chemical
Reg. No./Substance:
0/Cytokines; 0/Heat-Shock Proteins; 0/Hspb1 protein, mouse; 0/Intracellular Signaling Peptides and Proteins; 0/Lipopolysaccharides; 0/Neoplasm Proteins; EC 2.7.-/Protein Kinases; EC 2.7.1.-/MAP-kinase-activated kinase 2; EC 2.7.1.11/MAP-kinase-activated kinase 5; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.24/Mitogen-Activated Protein Kinases; EC 2.7.11.24/p38 Mitogen-Activated Protein Kinases
Comments/Corrections

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