Activation of the p21ras 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 p21ras results in egr-1 induction similar to that previously shown after antigen receptor cross-linking. In addition, both antigen receptor cross-linking and p21ras use the same element in the egr-1 promoter to exert their effects. Using dominant-negative mutants of p21ras and raf-1, we demonstrate that induction of egr-1 after antigen receptor cross-linking is mediated by activation of the p21ras/mitogen-activated protein kinase signaling pathway. While regulation of the p21ras pathway during B cell activation has been intensively studied, this report represents the first description of a biologically relevant event associated with its activation.
McMahon
S B
SB
Department of Pathology and Laboratory Medicine, School of Medicine, University of Pennsylvania, Philadelphia 19104.
Monroe
J G
JG
D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D001483:Base Sequence; D004268:DNA-Binding Proteins / Q000235:genetics*; D051766:Early Growth Response Protein 1; D005786:Gene Expression Regulation; D017874:Immediate-Early Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism*; D011947:Receptors, Antigen, B-Cell / Q000502:physiology*; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics*
D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; D017874:Immediate-Early Proteins; D011947:Receptors, Antigen, B-Cell; D014157:Transcription Factors; D016283:Proto-Oncogene Proteins p21(ras)