proteins, depending on the other factors involved and their specific interactions with each other. When studying signaling pathways, mutations can further highlight the importance of each component used to activate the downstream target. For instance, disruption of the C-terminal domain of Elk1 that MAPK phosphorylates triggers inhibition of c-fos activation. Similarly, dysfunctional SRF, which normally tethers Elk1 to the SRE, leads to Fos not being transcribed. At the same time, without Elk1, SRF cannot induce c-fos transcription after MAPK stimulation. For these reasons, Elk1 represents an essential link between signal transduction pathways and the initiation of gene transcription. Clinical significance Long-term memory Formation of long-term memory may be dependent on Elk1. MEK inhibitors block Elk1 phosphorylation and, thus, impair acquired conditioned taste aversion. Moreover, avoidance learning, which involves the subject learning that a particular response leads to prevention of an aversive stimulus, is correlated with a definite increase in activation of Erk, Elk1, and c-fos in the hippocampus. This area of the brain is involved in short-term and long-term information storage. When Elk1 or SRF binding to DNA is blocked in the rat hippocampus, only sequestration of SRF interferes with long-term spatial memory. While the interaction of Elk1 with DNA may not be essential for memory formation, its specific role still needs to be explored. This is because activation of Elk1 can trigger other molecular events that do not require Elk1 to bind DNA. For example, Elk1 is involved in the phosphorylation of histones, increased interaction with SRF, and recruitment of the basal transcriptional machinery, all of which do not require direct binding of Elk1 to DNA. Drug addiction Elk1 activation plays a central role in drug addiction. After mice are given cocaine, a strong and momentary hyperphosphorylation of Erk and Elk1 is observed in the striatum. When these mice are then given MEK inhibitors, Elk1 phosphorylation is absent. Without active Elk1, c-fos production and cocaine-induced conditioned place preference are shown to be blocked. Moreover, acute ethanol ingestion leads to excessive phosphorylation of Elk1 in the amygdala. Silencing of Elk1 activity has also been found to decrease cellular responses to withdrawal signals and lingering treatment of opioids, one of the world's oldest known drugs. Altogether, these results highlight that Elk1 is an important component of drug addiction. Pathophysiology Buildup of beta amyloid (Aβ) peptides is shown to cause and/or trigger Alzheimer's disease. Aβ interferes with BDNF-induced phosphorylation of Elk1. With