BASAL EXTRACELLULAR SIGNAL-REGULATED KINASE-ACTIVITY MODULATES CELL-CELL AND CELL-MATRIX INTERACTIONS

Suppression of the basal extracellular signal-regulated kinase (ERK) a ctivity in PC12 cells markedly altered their phenotype. Wild-type cell s grew in a dissociated pattern adherent to the substrate. The stable expression of an ERK inhibitory mutant resulted in the formation of ca lcium-dependent aggregates which were less adherent to the substrate. Concomitantly, the cells reorganized their actin cytoskeleton and incr eased their expression of several adherens junction proteins, particul arly 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 incre ased their expression of adherens junction proteins following treatmen t with the selective MEK inhibitor PD98059, A peptide containing the H AV cadherin recognition sequence attenuated the aggregation. These stu dies suggest that in PC12 and epithelial cells, ERKs are pivotally pos itioned to enhance substrate interactions when active or to release ho motypic interactions when suppressed.