Inhibition of HSP27 phosphorylation by a cell-permeant MAPKAP Kinase 2 inhibitor.

Lopes LB, Flynn C, Komalavilas P, Panitch A, Brophy CM, Seal BL
Biochem Biophys Res Commun. 2009 382 (3): 535-9

PMID: 19289101 · PMCID: PMC2745729 · DOI:10.1016/j.bbrc.2009.03.056

Heat shock protein 27 (HSP27) has been implicated in many intracellular signaling processes. Since the phosphorylation of HSP27 can modulate its activity, the ability to inhibit phosphorylation of HSP27 might have clinical relevance especially with regard to the treatment of fibrosis. We have developed a cell-permeant peptide inhibitor of MAPKAP Kinase 2 (MK2), an enzyme that phosphorylates HSP27, by combining a previously described peptide substrate of MK2 with a cell penetrating peptide. This novel MK2 inhibitor (MK2i) reduced HSP27 phosphorylation by MK2 in vitro. At 10 microM, MK2i inhibited TGF-beta1-induced HSP27 phosphorylation in serum-starved human keloid fibroblasts. In addition, 10 microM MK2i decreased TGF-beta1-induced expression of connective tissue growth factor and collagen type I within serum-starved keloid fibroblasts. Thus, MK2i represents a potential therapeutic for the treatment of fibrotic disorders.

MeSH Terms (12)

Amino Acid Sequence Cell Membrane Permeability Cells, Cultured HSP27 Heat-Shock Proteins Humans Intracellular Signaling Peptides and Proteins Molecular Sequence Data Peptides Phosphorylation Protein-Serine-Threonine Kinases Protein Kinase Inhibitors Transforming Growth Factor beta1

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