ISOLATION AND CHARACTERIZATION OF MURINE FRA-1 - INDUCTION MEDIATED BY CD40 AND SURFACE IG IS PROTEIN-KINASE-C DEPENDENT

The murine fra-1 gene, encoding Fos-related Ag 1, was isolated from a splenic cDNA library and sequenced, Murine fra-1 was highly homologous to rat and human fra-1. Oligonucleotide primers based on the murine s equence were used to construct a quantitative reverse transcription-PC R assay for gene expression, B lymphocyte stimulation via both CD40 an d surface Ig (sIg) receptors substantially induced fra-1 expression, a nd for bath receptors, induction was protein kinase C (PKC) dependent, This contrasts with induction of c-fos by both CD40 and sIg, which is PKC independent and indicates that CD40 is capable of signaling throu gh PKC or a closely related kinase. Induction of fra-1 following engag ement of CD40 did not require protein synthesis, suggesting that the P KC-dependent linkage between CD40 and fra-1 is direct. CD40-mediated f ra-1 induction did require tyrosine kinase activity, These results dem onstrate that CD40, like sIg, may employ PKC in producing select outco mes, that individual B cell receptors may signal downstream events via both PKC-dependent and PKC-independent pathways, and that multiple si gnal transduction pathways may be used to activate the expression of c losely related genes.