Journal
CELLULAR SIGNALLING
Volume 21, Issue 5, Pages 712-718Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.cellsig.2009.01.009
Keywords
F-actin; Hsp27; MAPKAP-kinase; PRAK; MK2; MK5
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Funding
- Norwegain Cancer Society (Kreftforeningen A5308 and A5313)
- Mohn Grant (Forskningsstiftelsen Tromso).
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Mitogen-activated protein kinase (MAPK) pathways can play a role in F-actin dynamics. In particular. the p38 MAPK/MAPK-activated protein kinase 2 (MK2)/heat shock protein 27 (Hsp27) pathway is involved in F-actin alternations. Previously, we showed that MK5 is implicated in F-actin rearrangement induced by the cAMP/cAMP-dependent protein kinase pathway in PC12 cells, while others found Hsp27 to be a good in vitro MK5 substrate. Here we demonstrate that MK5 can specifically interact with Hsp27 in vivo and can induce phosphorylation at serine residues 78 and 82 in cells. siRNA-mediated depletion of Hsp27 protein levels, as well as overexpression of the non-phosphorylatable Hsp27-3A mutant prevented forskolin-induced F-actin reorganization. While ectopic expression of a constitutive active MK5 mutant was sufficient to induce F-actin rearrangement in PC12 cells, co-expression of Hsp27-3A could ablate this process. Our results imply that MK5 is involved in Hsp27-controlled F-actin dynamics in response to activation of the cAMP-dependent protein kinase pathway. These findings render the MK5/Hsp27 connection into a putative therapeutic target for conditions with aberrant Hsp27 phosphorylation such as metastasis, cardiovascular diseases, muscle atrophy, autoimmune skin disease and neuropathology. (C) 2009 Elsevier Inc. All rights reserved.
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