ELK1

ELK1 is a transcription factor in the ETS family and a member of the ternary complex factors (TCFs). It participates in signaling pathways that regulate gene expression in response to growth factors, mitogens, and neuronal activity. In the nucleus, ELK1 cooperates with serum response factor (SRF) to control transcription from serum response elements (SREs) in target gene promoters, including many immediate-early genes.

ELK1 contains an ETS DNA-binding domain that recognizes ETS motifs and a transactivation region at the N-terminus. The ETS domain enables ELK1 to bind DNA, while its activation domain recruits coactivators and the transcriptional machinery. Through its interaction with SRF, ELK1 helps form a ternary complex that enhances transcription of target genes such as FOS and EGR1 in response to stimuli.

Activation of ELK1 is primarily driven by the mitogen-activated protein kinase (MAPK) signaling cascade, especially ERK1/2. Upon pathway activation, ERK1/2 phosphorylate ELK1, increasing its transcriptional activity and promoting recruitment of coactivators such as CBP/p300. This phosphorylation-dependent mechanism links extracellular signals to changes in gene expression.

Functions attributed to ELK1 include regulation of cell proliferation, differentiation, and migration, as well as participation in neuronal plasticity and activity-dependent gene expression. ELK1 activity is modulated by cross-talk with other signaling pathways and by alterations in chromatin state at target promoters.

ELK1 is evolutionarily conserved and is one of the vertebrate ETS family members linked to the broader family of ELK proteins (including ELK3 and ELK4) that mediate responses to extracellular signals. Dysregulation of ELK1 signaling has been associated with cancer and neurological processes, making it a focus of studies on signal-transduction–to–transcription mechanisms.