title: Vimentin dephosphorylation at ser-56 is regulated by type 1 protein phosphatase in smooth muscle.
abstract: The intermediate filament protein vimentin undergoes reversible phosphorylation and dephosphorylation at Ser-56, which plays an important role in regulating the contraction-relaxation cycles of smooth muscle. The protein phosphatases that mediate vimentin dephosphorylation in smooth muscle have not been previously investigated.
  
  
  
  The associations of protein phosphatase 1 (PP1) and protein phosphatase 2A (PP2A) with vimentin in mouse tracheal rings was evaluated by co-immunoprecipitation. Lentivirus-mediated shRNA against PP1 was used to assess the role of PP1 in vimentin dephosphorylation and the vimentin-associated process in smooth muscle.
  
  
  
  Co-immunoprecipitation analysis showed that vimentin interacted with PP1, but barely with PP2A, in airway smooth muscle. Knockdown of PP1 by lentivirus-mediated shRNA increased the acetylcholine-induced vimentin phosphorylation and smooth muscle contraction. Because vimentin phosphorylation is able to modulate p130 Crk-associated substrate (p130CAS) and actin polymerization, we also evaluated the role of PP1 in the biological processes. Silencing of PP1 also enhanced the agonist-induced the dissociation of p130CAS from vimentin and F/G-actin ratios (an index of actin polymerization). However, PP1 knockdown did not affect c-Abl tyrosine phosphorylation, an important molecule that controls actin dynamics.
  
  
  
  Taken together, these findings suggest that PP1 is a key protein serine/threonine phosphatase that controls vimentin Ser-56 dephosphorylation in smooth muscle. PP1 regulates actin polymerization by modulating the dissociation of p130CAS from vimentin, but not by affecting c-Abl tyrosine kinase.
authors.affiliation: Department of Molecular and Cellular Physiology, Albany Medical College, 47 New Scotland Avenue, MC-8, Albany, New York, USA.
authors.forename: Jia
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Molecular and Cellular Physiology, Albany Medical College, 47 New Scotland Avenue, MC-8, Albany, New York, USA.
authors.forename: Ruping
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Molecular and Cellular Physiology, Albany Medical College, 47 New Scotland Avenue, MC-8, Albany, New York, USA. tangd@mail.amc.edu.
authors.forename: Dale D
authors.initials: DD
authors.lastname: Tang
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D050719:Crk-Associated Substrate Protein / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D008810:Mice, Inbred C57BL; D009119:Muscle Contraction; D009130:Muscle, Smooth / Q000187:drug effects / Q000201:enzymology*; D018994:Myosin Light Chains / Q000378:metabolism; D019319:Okadaic Acid / Q000494:pharmacology; D010766:Phosphorylation; D011485:Protein Binding; D054645:Protein Phosphatase 1 / Q000235:genetics / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D016315:Proto-Oncogene Proteins c-abl / Q000378:metabolism; D034622:RNA Interference; D012694:Serine; D013997:Time Factors; D046509:Tissue Culture Techniques; D014132:Trachea / Q000187:drug effects / Q000201:enzymology*; D014162:Transfection; D014746:Vimentin / Q000378:metabolism*
chemical_list: D000199:Actins; C493842:Bcar1 protein, mouse; D050719:Crk-Associated Substrate Protein; D018994:Myosin Light Chains; D014746:Vimentin; D019319:Okadaic Acid; D012694:Serine; D016315:Proto-Oncogene Proteins c-abl; D054645:Protein Phosphatase 1