Basal extracellular signal-regulated kinase activity modulates cell-cell and cell-matrix interactions.
Suppression of the basal extracellular signal-regulated kinase (ERK) activity in PC12 cells markedly altered their phenotype. Wild-type cells grew in a dissociated pattern adherent to the substrate. The stable expression of an ERK inhibitory mutant resulted in the formation of calcium-dependent aggregates which were less adherent to the substrate. Concomitantly, the cells reorganized their actin cytoskeleton and increased their expression of several adherens junction proteins, particularly cadherin. Metabolic labeling demonstrated an increased synthesis of cadherin and beta-catenin in these cells. Nontransfected PC12 cells and a ras-transformed MDCK cell line also formed aggregates and increased their expression of adherens junction proteins following treatment with the selective MEK inhibitor PD98059. A peptide containing the HAV cadherin recognition sequence attenuated the aggregation. These studies suggest that in PC12 and epithelial cells, ERKs are pivotally positioned to enhance substrate interactions when active or to release homotypic interactions when suppressed.
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Center for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA 02115, USA.
Paredes
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Zhang
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Kosik
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D000199:Actins / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD; D015820:Cadherins / Q000096:biosynthesis; D002118:Calcium / Q000378:metabolism; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002450:Cell Communication; D002460:Cell Line; D003598:Cytoskeletal Proteins / Q000096:biosynthesis; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005109:Extracellular Matrix / Q000502:physiology*; D005419:Flavonoids / Q000494:pharmacology; D019950:Mitogen-Activated Protein Kinase 1; D016716:PC12 Cells; D010641:Phenotype; D051381:Rats; D015534:Trans-Activators; D051176:beta Catenin
D000199:Actins; D015703:Antigens, CD; C050361:CDH2 protein, human; D015820:Cadherins; D015815:Cell Adhesion Molecules; C495268:Ctnnb1 protein, rat; D003598:Cytoskeletal Proteins; D004791:Enzyme Inhibitors; D005419:Flavonoids; D015534:Trans-Activators; D051176:beta Catenin; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; D002118:Calcium