ELK3

ELK3, also known as Elk-3 or SAP-2, is a transcription factor in the ETS family. It is a member of the ternary complex factors (TCFs), which also includes ELK1 and ELK4. The protein contains an ETS DNA-binding domain that recognizes Ets motifs, allowing it to regulate genes downstream of mitogenic signaling.

ELK3 activity is regulated by the RAS–MAPK pathway. Upon growth-factor stimulus, ERK1/2 kinases phosphorylate Elk-3, modulating its transcriptional activity and interactions with co-regulators. In many contexts, Elk-3 partners with serum response factor (SRF) at serum response elements (SREs) in promoter regions to control the expression of immediate-early genes such as FOS and EGR1. The precise effect on transcription—activation or repression—depends on cellular context and the combination of cofactors present.

ELK3 is expressed in a broad range of tissues and participates in processes such as cell proliferation, differentiation, and migration. In development, Elk-3-related signaling contributes to vascular and tissue morphogenesis in model systems. In pathology, altered ELK3 signaling has been linked to cancer-related traits such as invasion and metastasis in some studies, though its roles are context-dependent and continue to be investigated.

In humans, the ELK3 gene is the genetic source of Elk-3; its expression is studied alongside its relatives ELK1 and ELK4, which share structural features and convergent regulatory pathways. The ELK3–SRF axis represents a node where MAPK signaling informs transcriptional programs that drive immediate-early gene expression.