Extracellular Signal-Regulated Kinase Promotes Rho-Dependent Focal Adhesion Formation by Suppressing p190A RhoGAP

Abstract

Cell migration is critical for normal development and for pathological processes including cancer cell metastasis. Dynamic remodeling of focal adhesions and the actin cytoskeleton are crucial determinants of cell motility. The Rho family and the mitogen-activated protein kinase (MAPK) module consisting of MEKextracellular signal-regulated kinase (ERK) are important regulators of these processes, but mechanisms for the integration of these signals during spreading and motility are incompletely understood. Here we show that ERK activity is required for fibronectin-stimulated Rho-GTP loading, Rho-kinase function, and the maturation of focal adhesions in spreading cells. We identify p190A RhoGAP as a major target for ERK signaling in adhesion assembly and identify roles for ERK phosphorylation of the C terminus in p190A localization and activity. These observations reveal a novel role for ERK signaling in adhesion assembly in addition to its established role in adhesion disassembly.

Connexin 32 and its derived homotypic gap junctional intercellular communication inhibit the migration and invasion of transfected HeLa cells via enhancement of intercellular adhesion

“…The role of the p38 and ERK1/2 MAPK pathways in the regulation of cell adhesion has been demonstrated by several studies (28,29). Most recently, the ERK MAPK pathway was shown to play a novel role in the dynamic remodeling of focal adhesions and the actin cytoskeleton, which are crucial determinants of cell motility (30). However, no studies have addressed the correlations between the p38 and ERK1/2 MAPK pathways and Cx-mediated changes in adhesion, migration and invasion.…”

HLA class I-mediated stress fiber formation requires ERK1/2 activation in the absence of an increase in intracellular Ca2+ in human aortic endothelial cells

“…MLCP dephosphorylates MLC and consequently acts as a negative regulator of actomyosin contraction (6,30,39,50,62). The activation of ERK1/2 has been linked to Rho activation through phosphorylation and inhibition of RhoGAP p190A, which increases Rho-GTP leading to MLC phosphorylation via ROK (44). A second mechanism of MLC regulation utilizes the Ca 2ϩ /calmodulin-dependent MLC kinase (MLCK) to induce stress fibers and depends on several factors, which include elevated intracellular Ca 2ϩ and protein kinase C activation.…”

Fgfr-Ras-MAPK signaling is required for apical constriction via apical positioning of Rho-associated kinase during mechanosensory organ formation

“…An intriguing question raised by this work is that of how FgfrRas-MAPK acts to regulate the apical localization of Rock2a. Although Rock does not contain a consensus sequence for MAPK phosphorylation, MAPK might regulate Rock via phosphorylation and suppression of p190A RhoGAP activity and subsequent promotion of RhoA/Rock activity (Pullikuth and Catling, 2010).…”