Phosphorylation of the small heat shock-related protein, HSP20, in vascular smooth muscles is associated with changes in the macromolecular associations of HSP20.
Cyclic nucleotide-dependent vasorelaxation is associated with increases in the phosphorylation of a small heat shock-related protein, HSP20. We hypothesized that phosphorylation of HSP20 in vascular smooth muscles is associated with alterations in the macromolecular associations of HSP20. Treatment of bovine carotid artery smooth muscles with the phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine, and the adenylate cyclase activator, forskolin, led to increases in the phosphorylation of HSP20 and dissociation of macromolecular aggregates of HSP20. However, 3-isobutyl-1-methylxanthine and forskolin treatment of a muscle that is uniquely refractory to cyclic nucleotide-dependent vasorelaxation, human umbilical artery smooth muscle, did not result in increases in the phosphorylation of HSP20 or to dissociation of macromolecular aggregates. HSP20 can be phosphorylated in vitro by the catalytic subunit of cAMP-dependent protein kinase (PKA) in both carotid and umbilical arteries and this phosphorylation of HSP20 is associated with dissociation of macromolecular aggregates of HSP20. Activation of cyclic nucleotide-dependent signaling pathways does not lead to changes in the macromolecular associations of another small heat shock protein, HSP27. Interestingly, the myosin light chains (MLC20) are in similar fractions as the HSP20, and phosphorylation of HSP20 is associated with changes in the macromolecular associations of MLC20. These data suggest that increases in the phosphorylation of HSP20 are associated with changes in the macromolecular associations of HSP20. HSP20 may regulate vasorelaxation through a direct interaction with specific contractile regulatory proteins.
Brophy
C M
CM
Department of Surgery, Medical College of Georgia, Augusta, Georgia 30912, USA. colleen@mail.mcg.edu
Dickinson
M
M
Woodrum
D
D
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D002417:Cattle; D005576:Colforsin / Q000494:pharmacology; D050886:HSP20 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010750:Phosphoproteins / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects
D050886:HSP20 Heat-Shock Proteins; C494382:HSPB6 protein, human; D006360:Heat-Shock Proteins; D010726:Phosphodiesterase Inhibitors; D010750:Phosphoproteins; D005576:Colforsin; D015056:1-Methyl-3-isobutylxanthine