(see reviews by Robertson and Dragunow 1990; Morgan and Curran 1991; 
Robertson et al. 1991a). 
IEG INDUCTION AND THE BRAIN 
Activation of lEGs is not a unique property of neurons; indeed, lEGs were first 
characterized in nonneuronal cells during attempts to identify genes that might 
respond to growth factors (Cochran et al. 1983). This resulted in the description 
of a class of genes whose transcription was rapidly (in minutes) but transiently 
(usually for a few hours at most) activated following growth factor application. 
Using differential screening of cDNA libraries from growth-factor stimulated 
cells, many lEGs have been characterized, and the number of these, now at 
about 100, continues to grow. In the absence of stimulation, the expression 
of lEGs is generally low. Following stimulation, transcriptional activation is 
rapid and transient, and the mRNAs transcribed from these genes often have 
short half-lives. The subsequent shutoff of transcription requires new protein 
synthesis; lEGs are therefore superinduced in the presence of protein synthesis 
inhibitors (Sheng and Greenberg 1990). The crucial step linking these growth- 
activated lEGs to neuronal events was accomplished when several groups at 
about the same time demonstrated that not only growth factors but also 
neurotransmitters and neurotransmitter-related events such as depolarization 
and calcium influx will induce transcription of lEGs both in cells in culture 
(Greenberg et al. 1985, 1986; Morgan and Curran 1986) and in the brain in 
vivo (Morgan et al. 1987; Hunt et al. 1987; Dragunow and Robertson 1987a). 
Since c -fos was originally thought to be involved in cell division, studies 
demonstrating c -fos induction in differentiated PC-12 cells and the discovery 
of fos activation in brain was important in suggesting that lEGs could have a 
function in postmitotic cells (Greenberg et al. 1986; Morgan et al. 1987; Hunt 
et al. 1987; Dragunow and Robertson 1987a). 
It is now clear from many studies that neurotransmitters and neuronal 
growth factors in several systems will induce expression of lEGs (table 1). 
Rapid c -fos induction occurs in PC-12 cells following application of elevated 
K + , the calcium channel agonist BAY K8644, or external Ba ++ (Curran and 
Morgan 1985; Morgan and Curran 1986; Sheng et al. 1988), suggesting that 
Ca ++ , entering through voltage-dependent Ca ++ channels and/or L-type Ca ++ 
channels, is the major second messenger regulating IEG expression. There 
is also evidence that Ca ++ -calmodulin-dependent protein kinases (CaM kinases) 
I and II play a role in the transduction of electrical signals to the nucleus, and 
CREB (the adenosine 3',:5'cyclic phosphate [cAMP] response element-binding 
protein) may function to integrate Ca ++ and cAMP signals (Morgan and Curran 
1986; Greenberg et al. 1985, 1986; Sheng et al. 1991). In addition, recent 
evidence suggests that AP-1 proteins may also have an important part to play 
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