Induced expression of a RhoA-specifiic guanine nucleotide exchange factor, p190RhoGEF, following CD40 stimulation and WEHI 231 B cell activation

Abstract

Stimulation of the B cell surface receptor CD40 induces transcriptional activation and protein expression. To determine which proteins are required for the CD40-mediated B cell activation, we performed a two-dimensional gel electrophoresis of the WEHI 231 B cell lysates. We report in this study the identification of one protein in which the expression was remarkably induced following CD40 stimulation. It was the p190 Rho guanine nucleotide exchange factor (GEF), p190RhoGEF, a recently identified GEF that is specific for RhoA, Overexpression of either p190RboGEF or hboA (Q63L), a constitutively active form of RboA, mimics the effects of CD40 stimulation, such as changes in cellular structure and NF-kappaB activation. These p190RhoGEF overexpression effects are abrogated when coexpressed with a dominant negative form of RboA (T19N), We also provide evidence for the CD40-mediated cellular changes that are abrogated in cells that are overexpressed with the dominant negative form of either p190RhoGEF (Y1003A) or RboA (T19N).