Advances in Pharmacological Sciences · 2008 · 13 citations · 34 references
Life SciencesPharmacologyPhysiologyCell SignalingPharmacodynamicsSignal TransductionCardiovascular Molecular PhysiologyCardiovascular PathophysiologyCardiovascular PhysiologyMuscle PhysiologyProtein Kinase CascadesPulmonary PhysiologyAngiotensin Receptor SignalingExtracellular Signal-regulated Kinase PathwayIsoelectric FocusingPhosphoinositide PhosphorylationSmooth Muscle ContractionVascular Smooth Muscle Cell PhysiologyVascular Smooth Muscle PharmacologyVascular Smooth Muscle Regulation
We hypothesized that agonist-induced contraction correlates with the phospho-cofilin/cofilin (P-CF/CF) ratio in pulmonary artery (PA) rings and cultured smooth muscle cells (PASMCs). PA rings were used for isometric contractions and along with PASMCs for assay of P-CF/CF by isoelectric focusing and immunoblotting. The P-CF/CF measured 22.5% in PA and differentiated PASMCs, but only 14.8% in undifferentiated PASMCs. With comparable contraction responses in PA, endothelin-1 (100 nM) and norepinephrine (1 μM) induced a 2-fold increase of P-CF/CF, while angiotensin II (1 μM) induced none. All agonists activated Rho-kinase and LIMK2, and activation was eliminated by inhibition of Rho-kinase. Microcystin LF (20 nM) potentiated the angiotensin II, but not the 5-hydroxytryptamine (1 μM)-mediated increase of P-CF/CF. In conclusion, all tested agonists activate the Rho-kinase-LIMK pathway and increase P-CF/CF. Angiotensin II activates PP2A and counteracts the LIMK-mediated CF phosphorylation. CF phosphorylation stabilizes peripheral actin structures and may contribute to the maximal contraction of PA.
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Signaling from Rho to the Actin Cytoskeleton Through Protein Kinases ROCK and LIM-kinase
Midori Maekawa, Toshimasa Ishizaki, Shuken Boku et al. · Science · 1999 · 1.6K citations