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

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.
Mesh Terms:
Actins, Animals, Cell Line, Colforsin, Cyclic AMP, Cyclic AMP-Dependent Protein Kinases, HSP27 Heat-Shock Proteins, Humans, Intracellular Signaling Peptides and Proteins, MAP Kinase Kinase 2, MAP Kinase Signaling System, PC12 Cells, Phosphorylation, Protein-Serine-Threonine Kinases, RNA, Small Interfering, Rats
Cell. Signal.
Date: May. 01, 2009
Download Curated Data For This Publication
195478
Switch View:
  • Interactions 5