Abstract
The AP1 transcriptional complex is a heterodimer composed of proteins encoded by the fos and jun proto‐oncogene families. Changes in the concentration and composition of AP1 occur after cells are perturbed in a variety of different ways (Curran, in Reddy et al., eds. “The Oncogene Handbook,” Amsterdam: Elsevier, pp 307–325, 1988; Sonnenberg et al., Neuron 3:359–365, 1989). Transient changes in AP1 conlent presumably result in altered expression of AP1‐regulated targel genes, that help to mediate the cell's long‐term response to changes in its environment. One factor that may be important in determining which target genes are regulated by AP1 in a given context is the identity of the jun family member present in the complex (Chiu et al., Cell 59:979–986, 1989; Schutte et al., Cell 59:987–997, 1989). Fos induction has been demonstrated after binding of β‐adrenergic ligands to their cell surface receptors (Barka et al., Mol Cell Biol 6:2984–2989, 1986; Gubits et al., Mol Brain Res 6:39–45, 1989; Arenander et al., J Neurosci Res 24:107–114, 1989; Mocchetti et al., Proc Natl Acad Sci USA 86:3891–3895, 1989). However, the response of the jun gene family to this treatment has not been reported. We have therefore examined the effect of β‐adrenergic receptor activation on the expression of c‐fos, c‐jun, and junB mRNA levels in C6 glioma cells. Our results indicate that c‐fos and junB mRNA levels are increased by 52‐ and 2.7‐fold, respectively, after 45 min of isoproterenol (IPR) treatment. Unexpectedly, we found a concomitant decrease in c‐jun mRNA levels of about 2.5‐fold. The changes in c‐fos and c‐jun mRNAs were found to be dose dependent and specifically mediated by β‐ rather than alpha‐adrenergic receptors. The alterations in AP1 composition implied by our findings suggest a role for this transcriptional complex in mediating late gene responses lo β‐adrenergic receptor activation.