A role for MAP kinase in differentiated smooth muscle contraction evoked by alpha-adrenoceptor stimulation.
The purpose of this study was to investigate the potential role of mitogen-activated protein (MAP) kinase in smooth muscle contraction by monitoring MAP kinase activation, caldesmon phosphorylation, and contractile force during agonist stimulation. Isometric tension in response to KCl and phenylephrine (PE) was measured from strips of ferret aorta. MAP kinase activation was monitored by Western blot using a phosphospecific p44/p42 MAP kinase antibody. Caldesmon phosphorylation was assessed using specific phosphocaldesmon antibodies. We report here that treatment of smooth muscle strips with PD-098059, a specific inhibitor of MAP kinase kinase, did not detectably modify the KCl-evoked contraction but significantly inhibited the contraction to PE in the absence of extracellular Ca2+. In this experimental condition, where the contraction occurs in the absence of increases in 20-kDa myosin light chain phosphorylation, PD-098059 also inhibited significantly MAP kinase and caldesmon phosphorylation. Collectively, these results demonstrate a direct cause-and-effect relationship between MAP kinase activation and Ca2+-independent smooth muscle contraction and support the concept of caldesmon phosphorylation as the missing link between both events.
Dessy
C
C
Signal Transduction Group, Boston Biomedical Research Institute, Boston MA 02114, USA.
Kim
I
I
Sougnez
C L
CL
Laporte
R
R
Morgan
K G
KG
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D001011:Aorta; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002148:Calmodulin-Binding Proteins / Q000378:metabolism; D005289:Ferrets; D005419:Flavonoids / Q000494:pharmacology; D066298:In Vitro Techniques; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3; D020929:Mitogen-Activated Protein Kinase Kinases; D020928:Mitogen-Activated Protein Kinases; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D010656:Phenylephrine / Q000494:pharmacology*; D010766:Phosphorylation; D011189:Potassium Chloride / Q000494:pharmacology; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000378:metabolism; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*
D000316:Adrenergic alpha-Agonists; D002148:Calmodulin-Binding Proteins; D005419:Flavonoids; D047428:Protein Kinase Inhibitors; D011942:Receptors, Adrenergic, alpha; D010656:Phenylephrine; D011189:Potassium Chloride; D011494:Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one