The Small GTPase Ras Is Involved in Growth Factor-Regulated Expression of the α1 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, cellmatrix interactions mediated by integrins, as well as integrininduced signaling, are also involved in growth factorstimulated signal transduction in PC12 cells. In this study we determined the expression of the α1 integrin subunit in response to EGF and NGF in PC12 wildtype (wt) cells, and in PC12 cells overexpressing an inactive HRas protein (RasN17). In PC12 wt cells, α1 integrin expression is upregulated by EGF and NGF. Cell surface expression of α1β1 integrin is also enhanced in growth factortreated cells. This upregulation leads to increased α1β1- specific adhesion to collagen. In cells expressing the dominantnegative RasN17 variant, α1 integrin expression and α1β1-specific adhesion remain unchanged in response to both growth factors.