title: MAPK-activated protein kinase-2 (MK2)-mediated formation and phosphorylation-regulated dissociation of the signal complex consisting of p38, MK2, Akt, and Hsp27.
abstract: The p38 MAPK and heat shock protein 27 (hsp27) form a signaling complex with serine/threonine kinase Akt and MAPK-activated protein kinase-2 (MK2), which plays an important role in controlling stress-induced apoptosis and reorganizing actin cytoskeleton. However, regulation of the complex is poorly understood. In this study, the interaction between p38 and hsp27 was visualized in single living L929 cells using fluorescence resonance energy transfer technology, while their association with Akt was examined by immunoprecipitation analysis. Under normal growth conditions, p38 kinase constitutively interacts with hsp27. When cells were exposed to H(2)O(2) or stimulated by arachidonic acid, this interaction was disrupted. However, inhibition of the activation of p38 and Akt by selective inhibitors or overexpression of the kinase-dead mutant of p38 diminished such effects. Furthermore, mutation of phosphorylation sites of hsp27 renders the interaction resistant to H(2)O(2) and arachidonic acid. It was interesting to find that the interaction disappeared in the cells from MK2-knock-out mice or the cells treated with lemptomycin B that blocks export of MK2 from nucleus to cytosol. However, MK2 is not required for the association of hsp27 with Akt. This study suggests that MK2 mediates the incorporation of p38 into the pre-existing complex of hsp27 with Akt. Phosphorylation of hsp27 finally breaks the signaling complex.
authors.affiliation: Institute of Biophysics, and Graduate School, Chinese Academy of Sciences, 15 Datun Road, Choayang District, Beijing 100101, China.
authors.forename: Chunlei
authors.initials: C
authors.lastname: Zheng
authors.forename: Ziyang
authors.initials: Z
authors.lastname: Lin
authors.forename: Zhizhuang Joe
authors.initials: ZJ
authors.lastname: Zhao
authors.forename: Yajun
authors.initials: Y
authors.lastname: Yang
authors.forename: Hanben
authors.initials: H
authors.lastname: Niu
authors.forename: Xun
authors.initials: X
authors.lastname: Shen
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis; D016718:Arachidonic Acid / Q000494:pharmacology; D002460:Cell Line; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D055551:HSP27 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000502:physiology*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D018345:Mice, Knockout; D018832:Molecular Chaperones; D009363:Neoplasm Proteins / Q000502:physiology*; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*; D000099190:MAP-Kinase-Activated Kinase 2
chemical_list: D000903:Antibiotics, Antineoplastic; D016718:Arachidonic Acid; D005231:Fatty Acids, Unsaturated; D055551:HSP27 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D006861:Hydrogen Peroxide; D047908:Intracellular Signaling Peptides and Proteins; D018832:Molecular Chaperones; D009363:Neoplasm Proteins; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D048051:p38 Mitogen-Activated Protein Kinases; D000099190:MAP-Kinase-Activated Kinase 2; C057725:HSPB1 protein, human; C038753:leptomycin B