Cutting edge: induced expression of a RhoA-specific guanine nucleotide exchange factor, p190RhoGEF, following CD40 stimulation and WEHI 231 B cell activation.
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 p190RhoGEF or RhoA (Q63L), a constitutively active form of RhoA, 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 RhoA (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 RhoA (T19N).
Lee
Jong Ran
JR
Division of Molecular Life Sciences and Center for Cell Signaling Research, College of Natural Sciences, Ewha Womans University, Seoul, Korea. jrlee@mm.ewha.ac.kr
Ha
Yun Jung
YJ
Kim
Hye Jin
HJ
D000276:Adjuvants, Immunologic / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D019013:CD40 Antigens / Q000494:pharmacology*; D048429:Cell Size / Q000276:immunology; D002478:Cells, Cultured; D004268:DNA-Binding Proteins; D020690:GTPase-Activating Proteins; D005822:Genetic Vectors; D020662:Guanine Nucleotide Exchange Factors / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins; D014162:Transfection; D014407:Tumor Cells, Cultured; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
D000276:Adjuvants, Immunologic; C513041:Arhgap35 protein, mouse; C513042:Arhgap5 protein, mouse; D019013:CD40 Antigens; D004268:DNA-Binding Proteins; D020690:GTPase-Activating Proteins; D020662:Guanine Nucleotide Exchange Factors; D016328:NF-kappa B; D009687:Nuclear Proteins; D012097:Repressor Proteins; D020742:rhoA GTP-Binding Protein