ACTIVATION OF THE P21(RAS) PATHWAY COUPLES ANTIGEN RECEPTOR STIMULATION TO INDUCTION OF THE PRIMARY RESPONSE GENE EGR-1 IN B-LYMPHOCYTES

The primary response gene egr-1 encodes a sequence-specific transcription factor whose expression is necessary for antigen receptor-stimulated activation of B lymphocytes. The molecular processes involved in linking egr-1 induction to antigen receptor signaling have not been defined. The present study demonstrates that expression of an activated form of p21(ras) results in egr-1 induction similar to that previously shown after antigen receptor cross-linking. In addition, both antigen receptor cross-linking and P21(ras) use the same element in the egr-1 promoter to exert their effects. Using dominant-negative mutants of p21(ras) and raf-1, we demonstrate that induction of egr-1 antigen receptor cross-linking is mediated by activation of the p21(ras)/mitogen-activated protein kinase signaling pathway. While regulation of the p21(ras) pathway during B cell activation has been intensively studied, this report represents the first description of a biologically relevant event associated with its activation.