TABLE 1 . Some neurotransmitters involved in activation of lEGs 
Neurotransmitter 
Cell or Tissue 
Reference 
Glutamate 
Cholinergic (nicotinic) 
Cholinergic (muscarinic) 
Dopamine (D1, D5?) 
Adenosine 
Nerve growth factor (NGF) 
Cerebellar neurons 
Szekely et al. 1989 
Greenberg et al. 1985 
Morgan and Curran 1986 
Robertson et al. 1989a, 1989b 
Gubits et al. 1990 
Greenberg et al. 1985 
Haas et al. 1991 
PC-12 
PC-12 
Striatal neurons 
Neuron-glia hybrids 
PC-12 
Calcitonin gene-related peptide Rat astrocytes 
in activation and inhibition of gene expression by cAMP. Thus, Jun-D and 
Jun-B may be important in the regulation of the proenkephalin expression 
by the cAMP response element (Kobierski et al. 1991), emphasizing the 
importance of differential regulation of lEGs in control of gene expression. 
lEGs: DIFFERENTIAL REGULATION 
The situation is clearly more complicated in that many lEGs are simultaneously 
activated by physiological stimulation, neurotransmitters, and growth factors. It 
has been suggested that various combinations of lEGs could confer specificity 
of cell response to different stimuli (Sonnenberg et al. 1989; Sheng and 
Greenberg 1990; Wisden et al. 1990; Moratalla et al. 1992; Rusak et al., in 
press), although there is little or no evidence for this idea. 
The best known example of regulatory interaction between lEGs is the 
interactions between the fos and jun families. Protein products of members 
of these two IEG families can interact with each other to form heterodimeric 
transcriptional factor complexes via a conserved dimerization domain called 
the leucine zipper. Briefly, the protein c-Fos dimerizes with c-Jun to form a 
c-Fos/c-Jun transcriptional factor that binds with high affinity and specificity 
to DNA elements of the consensus sequence TGACTCA (the AP-1 site) 
and, thus, leads to the transcription of nearby promoters by an unknown 
mechanism (Curran and Franza 1988). However, it is clear that the situation 
is even more complicated than many lEGs activating transcription because 
some heterodimeric combinations are transcriptional inhibitors. The 
heterodimer formed by c-Fos and Jun-B (the protein product of the jun family 
member, Jun-B) represses transcription of genes with AP-1 sites in the 
promoter region (Chiu et al. 1989; Schutte et al. 1989). Moreover, the situation 
is made more complicated by the fact that c-Jun is an efficient activator of the 
c -jun promoter, whereas Jun-B inhibits activation of the c-jun promoter. Thus, 
57 
