Growth Factor Activity of Endothelin-1 in Primary Astrocytes Mediated by Adhesion-Dependent and -Independent Pathways

摘要: Endothelin-1 (ET-1) has been shown to induce DNA synthesis in primary astrocytes by stimulating the extracellular signal-regulated kinase (ERK) pathway. To clarify mechanisms responsible for anchorage-dependent growth of astrocytes, relationships between cell adhesion and ERK activation were investigated. Here it is reported that ET-1 promotes formation stress fibers focal adhesions tyrosine phosphorylation (FAK) paxillin, as well Src association phosphorylated FAK with Grb2. Pretreatment cytochalasin D or C3-transferase, which inhibits actin polymerization Rho activity, respectively, prevented activation/phosphorylation Src, FAK, paxillin after stimulation; contrast, pathway was not significantly affected. This differential FAK/Src pathways also observed 10 60 min replating on poly-l-ornithine-precoated dishes. Collectively, these findings indicate dependent cytoskeleton integrity, activation, matrix, whereas independent intracellular events seems correlate newly identified protein PYK2. Induction ET-1, however, reduced dramatically pretreated either C3-transferase. study provides a demonstration Rho- adhesion-dependent FAK/Src, collaborates adhesion-independent PYK2/ERK ET-1-stimulated astrocytes.