PKA-induced F-actin rearrangement requires phosphorylation of Hsp27 by the MAPKAP kinase MK5.

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Kostenko S, Johannessen M, Moens U

PKA-induced F-actin rearrangement requires phosphorylation of Hsp27 by the MAPKAP kinase MK5.

Cell Signal. 2009 May;21(5):712-8. doi: 10.1016/j.cellsig.2009.01.009. Epub 2009 Jan 8.

PubMed ID
19166925 [ View in PubMed
]
Abstract

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.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Heat shock protein beta-1P04792Details
MAP kinase-activated protein kinase 5Q8IW41Details