The small Gtpase ras is involved in growth factor-regulated expression of the alpha1 integrin subunit in PC12 cells

Abstract

PC12 cells interact with several growth factors (e. g. EGF, FGF, and NGF) via specific tyrosine receptor kinases, resulting in cell proliferation or neuronal differentiation. The small GTPase Ras is known to be involved in downstream signaling of these growth factor receptors. Furthermore, cell-matrix interactions mediated by integrins, as well as integrin-induced signaling, are also involved in growth factor-stimulated signal transduction in PC12 cells. In this study we determined the expression of the alpha1 integrin subunit in response to EGF and NGF in PC12 wild-type (wt) cells, and in PC12 cells overexpressing an inactive H-Ras protein (RasN17). In PC12 wt cells, alpha1 integrin expression is upregulated by EGF and NGF. Cell surface expression of alpha1beta1integrin is also enhanced in growth factor-treated cells. This upregulation leads to increased alpha1beta1-specific adhesion to collagen. In cells expressing the dominant-negative RasN17 variant, alpha1 integrin expression and alpha1beta1-specific adhesion remain unchanged in response to both growth factors.