title: Mitogen-activated protein kinase phosphatase-1 in rat arterial smooth muscle cell proliferation.
abstract: Smooth muscle cell proliferation and migration is important in arteriosclerosis. In this process, cytokines and growth factors are upregulated and bind to their respective receptors, which in turn stimulate mitogen-activated protein (MAP) kinases. MAP kinases then relay signals to the nucleus that activate quiescent smooth muscle cells. Phosphatases downregulate MAP kinases. We investigated the role of a dual-specificity tyrosine phosphatase, MAP kinase phosphatase-1 (MKP-1), in smooth muscle cell proliferation. MKP-1 expression was high in arterial tissue by Northern analysis, and MKP-1 message was detected mainly in the arterial smooth muscle layer by in situ hybridization. After balloon injury of the rat carotid artery, expression of MKP-1 decreased greatly, whereas that of MAP kinases, especially p44 MAP kinase, increased. The time course of the reduction in MKP-1 message correlated with increased tyrosine phosphorylation and elevated p44 MAP kinase enzymatic activity. In rat arterial smooth muscle cells overexpressing MKP-1, growth was arrested in the G1 phase and entry into the S phase was blocked. A reduction in MKP-1 expression may contribute in part to proliferation of smooth muscle cells after vascular injury, possibly through a decrease in dephosphorylation of p44 MAP kinase.
authors.affiliation: Cardiovascular Biology Laboratory, Harvard School of Public Health, Boston, Massachusetts 02115. USA.
authors.forename: K
authors.initials: K
authors.lastname: Lai
authors.forename: H
authors.initials: H
authors.lastname: Wang
authors.forename: W S
authors.initials: WS
authors.lastname: Lee
authors.forename: M K
authors.initials: MK
authors.lastname: Jain
authors.forename: M E
authors.initials: ME
authors.lastname: Lee
authors.forename: E
authors.initials: E
authors.lastname: Haber
mesh_terms: D000800:Angioplasty, Balloon; D000818:Animals; D001158:Arteries / Q000166:cytology* / Q000201:enzymology / Q000254:growth & development / Q000293:injuries; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002339:Carotid Arteries / Q000166:cytology / Q000201:enzymology; D020212:Carotid Artery Injuries; D002453:Cell Cycle; D018797:Cell Cycle Proteins; D054638:Dual Specificity Phosphatase 1; D015971:Gene Expression Regulation, Enzymologic; D017874:Immediate-Early Proteins / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D024510:Muscle Development; D009131:Muscle, Smooth, Vascular / Q000201:enzymology / Q000254:growth & development*; D009924:Organ Culture Techniques; D010749:Phosphoprotein Phosphatases; D010766:Phosphorylation; D054645:Protein Phosphatase 1; D017027:Protein Tyrosine Phosphatases / Q000096:biosynthesis* / Q000235:genetics; D011651:Pulmonary Artery / Q000166:cytology / Q000201:enzymology / Q000254:growth & development; D051381:Rats; D011994:Recombinant Proteins / Q000096:biosynthesis; D014018:Tissue Distribution
chemical_list: D018797:Cell Cycle Proteins; D017874:Immediate-Early Proteins; D011994:Recombinant Proteins; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; D054638:Dual Specificity Phosphatase 1; C517021:Dusp1 protein, rat; D017027:Protein Tyrosine Phosphatases