Differential increase of an alternatively polyadenylated mRNA species of murine CD40 upon B lymphocyte activation.
CD40 is an integral membrane glycoprotein found on the surface of human B lymphocytes. Antibodies specific for CD40 have been shown to augment proliferation of activated B lymphocytes, prevent B lymphocyte apoptosis, and prolong the maintenance of normal B lymphocytes in culture. As a step toward developing an in vivo system to examine CD40 function, a molecular clone encoding the murine homologue of the human CD40 B lymphocyte surface Ag was isolated and characterized. Throughout their open reading frames, the murine and human proteins shared 62% predicted amino acid identity. Within the cytoplasmic domain, which includes a completely conserved region known to be important for signaling by human CD40, the CD40 homologues are 78% identical. The human and murine proteins are members of a new cytokine receptor family, which includes the receptors for nerve growth factor and TNF-alpha, that are homologous in their cysteine-rich extracellular domains. The murine CD40 gene is expressed in B lymphocytes as two mRNA species generated by alternative usage of polyadenylation signals in the 3' untranslated region. The activation of B lymphocytes differentially increases the relative levels of these two mRNA transcripts suggesting a posttranscriptional mechanism for the regulation of CD40 surface expression.
Department of Microbiology SC-42, University of Washington, Seattle 98195.
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RM
Torres
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EA
Clark
D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000235:genetics*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000235:genetics*; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D001483:Base Sequence; D019013:CD40 Antigens; D004247:DNA / Q000302:isolation & purification; D005786:Gene Expression Regulation; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D011061:Poly A / Q000032:analysis*; D012333:RNA, Messenger / Q000032:analysis*; D014158:Transcription, Genetic
D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D019013:CD40 Antigens; D012333:RNA, Messenger; D011061:Poly A; D004247:DNA