title: PHI-1 interacts with the catalytic subunit of myosin light chain phosphatase to produce a Ca(2+) independent increase in MLC(20) phosphorylation and force in avian smooth muscle.
abstract: In avian smooth muscles, GTPgammaS produces a Rho kinase mediated increase in PHI-1 phosphorylation and force, but whether this correlation is causal is unknown. We examined the effect of phosphorylated PHI-1 (P-PHI-1) on force and myosin light chain (MLC(20)) phosphorylation at a constant [Ca(2+)]. P-PHI-1, but not PHI-1, increased MLC(20) phosphorylation and force, and phosphorylation of PHI-1 increased the interaction of PHI-1 with PP1c. Microcystin induced a dose-dependent reduction in the binding of PHI-1 to PP1c. These results suggest PHI-1 inhibits myosin light chain phosphatase by interacting with the active site of PP1c to produce a Ca(2+) independent increase in MLC(20) phosphorylation and force.
authors.affiliation: Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Amr
authors.initials: A
authors.lastname: El-Toukhy
authors.forename: Allison M
authors.initials: AM
authors.lastname: Given
authors.forename: Ozgur
authors.initials: O
authors.lastname: Ogut
authors.forename: Frank V
authors.initials: FV
authors.lastname: Brozovich
mesh_terms: D000818:Animals; D030161:Avian Proteins / Q000378:metabolism*; D002118:Calcium / Q000494:pharmacology*; D020134:Catalytic Domain; D002645:Chickens; D020559:Monomeric GTP-Binding Proteins / Q000378:metabolism; D009130:Muscle, Smooth / Q000378:metabolism*; D018994:Myosin Light Chains / Q000378:metabolism*; D043263:Myosin-Light-Chain Phosphatase / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding; D054645:Protein Phosphatase 1; D015398:Signal Transduction
chemical_list: D030161:Avian Proteins; D018994:Myosin Light Chains; D010750:Phosphoproteins; D054645:Protein Phosphatase 1; D043263:Myosin-Light-Chain Phosphatase; D020559:Monomeric GTP-Binding Proteins; D002118:Calcium