scholarly journals Inhibition of vascular smooth muscle growth via signaling crosstalk between AMP-activated protein kinase and cAMP-dependent protein kinase

2012 ◽  
Vol 3 ◽  
Author(s):  
Joshua D. Stone ◽  
Avinash Narine ◽  
David A. Tulis
Keyword(s):  
Smooth Muscle ◽  
Protein Kinase ◽  
Vascular Smooth Muscle ◽  
Muscle Growth ◽  
Dependent Protein Kinase ◽  
Signaling Crosstalk ◽  
Camp Dependent Protein Kinase ◽  
Dependent Protein ◽  
Amp Activated Protein Kinase

scholarly journals Regulation of vascular smooth muscle growth by cyclic nucleotides and cGMP-dependent protein kinase

2005 ◽  
Vol 5 (Suppl 1) ◽  
pp. P62 ◽  
Author(s):  
Pascal Weinmeister ◽  
Robert Lukowski ◽  
Stefan Linder ◽  
Wolfgang Erl ◽  
Richard Brandl ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Protein Kinase ◽  
Vascular Smooth Muscle ◽  
Cyclic Nucleotides ◽  
Muscle Growth ◽  
Dependent Protein Kinase ◽  
Cgmp Dependent Protein Kinase ◽  
Dependent Protein

PI3-kinase/Akt modulates vascular smooth muscle tone via cAMP signaling pathways

2001 ◽  
Vol 91 (4) ◽  
pp. 1819-1827 ◽  
Author(s):  
Padmini Komalavilas ◽  
Shyamal Mehta ◽  
Christopher J. Wingard ◽  
Daniel T. Dransfield ◽  
Jyoti Bhalla ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Protein Kinase ◽  
Vascular Smooth Muscle ◽  
Cyclic Nucleotide ◽  
Muscle Tone ◽  
Pi3 Kinase ◽  
Dependent Protein Kinase ◽  
Smooth Muscle Tone ◽  
Dependent Protein ◽  
Vascular Smooth Muscle Tone

Phosphatidylinositol 3-kinase (PI3-kinase) activates protein kinase B (also known as Akt), which phosphorylates and activates a cyclic nucleotide phosphodiesterase 3B. Increases in cyclic nucleotide concentrations inhibit agonist-induced contraction of vascular smooth muscle. Thus we hypothesized that the PI3-kinase/Akt pathway may regulate vascular smooth muscle tone. In unstimulated, intact bovine carotid artery smooth muscle, the basal phosphorylation of Akt was higher than that in cultured smooth muscle cells. The phosphorylation of Akt decreases in a time-dependent manner when incubated with the PI3-kinase inhibitor, LY-294002. Agonist (serotonin)-, phorbol ester (phorbol 12,13-dibutyrate; PDBu)-, and depolarization (KCl)-induced contractions of vascular smooth muscles were all inhibited in a dose-dependent fashion by LY-294002. However, LY-294002 did not inhibit serotonin- or PDBu-induced increases in myosin light chain phosphorylation or total O2 consumption, suggesting that inhibition of contraction was not mediated by reversal or inhibition of the pathways that lead to smooth muscle activation and contraction. Treatment of vascular smooth muscle with LY-294002 increased the activity of cAMP-dependent protein kinase and increased the phosphorylation of the cAMP-dependent protein kinase substrate heat shock protein 20 (HSP20). These data suggest that activation of the PI3-kinase/Akt pathway in unstimulated smooth muscle may modulate vascular smooth muscle tone (allow agonist-induced contraction) through inhibition of the cyclic nucleotide/HSP20 pathway and suggest that cyclic nucleotide-dependent inhibition of contraction is dissociated from the myosin light chain contractile regulatory pathways.

iNOS regulation by calcium/calmodulin-dependent protein kinase II in vascular smooth muscle

2007 ◽  
Vol 292 (6) ◽  
pp. H2634-H2642 ◽  
Author(s):  
Rachel J. Jones ◽  
David Jourd'heuil ◽  
John C. Salerno ◽  
Susan M. E. Smith ◽  
Harold A. Singer
Keyword(s):  
Smooth Muscle ◽  
Protein Kinase ◽  
Vascular Smooth Muscle ◽  
Resting Cells ◽  
Dependent Manner ◽  
Dependent Protein Kinase ◽  
Cytokine Induction ◽  
Calcium Calmodulin Dependent ◽  
Protein Kinase Ii ◽  
Dependent Protein

Nitric oxide synthase (NOS) expression is regulated transcriptionally in response to cytokine induction and posttranslationally by palmitoylation and trafficking into perinuclear aggresome-like structures. We investigated the effects of multifunctional calcium/calmodulin-dependent protein kinase II protein kinase (CaMKII) on inducible NOS (iNOS) trafficking in cultured rat aortic vascular smooth muscle cells (VSMCs). Immunofluorescence and confocal microscopy demonstrated colocalization of iNOS and CaMKIIδ2 with a perinuclear distribution and concentration in aggresome-like structures identified by colocalization with γ-tubulin. Furthermore, CaMKIIδ2 coimmunoprecipitated with iNOS in a CaMKII activity-dependent manner. Addition of Ca2+-mobilizing stimuli expected to activate CaMKII; a purinergic agonist (UTP) or calcium ionophore (ionomycin) caused a general redistribution of iNOS from cytosolic to membrane and nuclear fractions. Similarly, adenoviral expression of a constitutively active CaMKIIδ2 mutant altered iNOS localization, shifting iNOS from the cytosolic fraction. Suppression of CaMKIIδ2 using an adenovirus expressing a short hairpin, small interfering RNA increased nuclear iNOS localization in resting cells but inhibited ionomycin-induced translocation of iNOS to the nucleus. Following addition of these chronic and acute CaMKII modulators, there were fewer aggresome-like structures containing iNOS. All of the treatments that chronically affected CaMKII activity or expression significantly inhibited iNOS-specific activity following cytokine induction. The results suggest that CaMKIIδ2 may be an important regulator of iNOS trafficking and activity in VSMCs.

Calmodulin-dependent myosin light chain kinases from cardiac and smooth muscle: a comparative study

1980 ◽  
Vol 58 (4) ◽  
pp. 299-308 ◽  
Author(s):  
Michael P. Walsh ◽  
Jean-Claude Cavadore ◽  
Bernard Vallet ◽  
Jacques G. Demaille
Keyword(s):  
Smooth Muscle ◽  
Protein Kinase ◽  
Light Chain ◽  
Myosin Light Chain ◽  
Phosphorylation Site ◽  
Dependent Protein Kinase ◽  
Proteolytic Fragment ◽  
Cardiac Enzyme ◽  
Camp Dependent Protein Kinase ◽  
Dependent Protein

Various properties of cardiac and smooth muscle calmodulin-dependent myosin light chain kinases (MLCKs) have been compared. The enzymes exhibit the same isoelectric point (6.5) but differ markedly in molecular weight (Mr = 72 000 for both canine and bovine cardiac MLCK, and Mr = 130 000 for smooth muscle MLCK). Comparison of the tryptic peptide maps of bovine cardiac and turkey gizzard MLCKs indicates that the cardiac enzyme is a fragment of a protein homologous to the smooth muscle kinase. While the smooth muscle kinase can be phosphorylated by the catalytic subunit of cAMP-dependent protein kinase, the same is not true for either bovine or canine cardiac MLCK. Controlled tryptic hydrolysis of phosphorylated smooth muscle MLCK, followed by affinity chromatography on a column of calmodulin–Sepharose, enables separation of a phosphopeptide (Mr = 22 000) from a mixture of peptides of Mr = 50 000 and 24 000 which are bound to the column in the presence of Ca2+ and eluted with ethylene glycol bis(β-aminoethyl ether)-N,N′-tetraacetic acid. The phosphorylation site, therefore, is distinct from the calmodulin-binding site. It appears that cardiac MLCK is proteolyzed during the isolation procedure. The purified cardiac enzyme represents a proteolytic fragment which retains Ca2+ and calmodulin dependence but only a fraction of the specific activity of the native enzyme, and has lost the site of phosphorylation by cAMP-dependent protein kinase. A protease is shown to exist in myocardium which is capable of digesting smooth muscle MLCK rapidly at low temperature, and which is resistant to classical antiproteases.

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