VRKs

VRKs, short for Vaccinia-related kinases, are a small family of serine/threonine protein kinases found in eukaryotes. In humans the family comprises VRK1, VRK2, and VRK3. They share a conserved catalytic kinase domain and differ in regulatory regions that influence localization and substrate selection.

VRK1 is predominantly nuclear and expressed in proliferating cells, where it participates in cell cycle regulation and chromatin dynamics. VRK2 exists as two splice variants with distinct subcellular distributions, providing broader signaling potential. VRK3 is generally considered catalytically less active and can modulate VRK1 signaling and downstream pathways. Collectively, VRKs act on multiple substrates, including transcription factors and histones, linking phosphorylation events to transcriptional control, chromatin remodeling, and DNA damage responses.

Functionally, VRKs contribute to early steps of the cellular response to DNA damage, cell cycle checkpoints, and developmental processes. Through phosphorylation of substrates such as p53 and histone H3, they influence cell fate decisions, proliferation, and differentiation. Their activity is regulated by expression levels, localization, and interactions with other kinases and phosphatases.

Clinical relevance: Altered expression or mutations in VRK genes have been observed in various cancers and neurodevelopmental conditions. In research contexts, VRK1 has been linked to p53-mediated signaling and cell cycle control, making it a focus of studies on tumor biology and brain development.

Discovery and naming: The VRK family is named for sequence similarity to vaccinia virus kinases and is conserved across metazoans, with ongoing studies to clarify the full spectrum of substrates and physiological roles.