Disease relevance of VRK2

• Therefore, a cDNA library derived from normal human foreskin keratinocytes was screened by the yeast two-hybrid system and a cellular gene encoding human vaccinia virus B1R kinase-related kinase 2 (VRK2) was isolated [1].
• Human cellular protein VRK2 interacts specifically with Epstein-Barr virus BHRF1, a homologue of Bcl-2, and enhances cell survival [1].

High impact information on VRK2

• VRK1 proteins possess a basic nuclear localization signal and are indeed nuclear; the extreme C termini of the VRK2 proteins are highly hydrophobic, and the proteins are membrane-associated and colocalize with markers of the endoplasmic reticulum [2].
• This mammalian kinase family comprises three members, VRK1, VRK2, and VRK3 [2].
• Overexpressed VRK2 alone showed a modest effect in anti-apoptosis and appeared to enhance cell survival in the presence of BHRF1 [1].
• Interaction between the cellular VRK2 and viral BHRF1 proteins was further demonstrated by glutathione S-transferase pull-down assays, confocal laser-scanning microscopy and co-immunoprecipitation [1].
• The results indicate that human VRK2 interacts specifically with EBV BHRF1 and that the interaction is involved in protecting cells from apoptosis [1].

Chemical compound and disease context of VRK2

• Identification of two novel human putative serine/threonine kinases, VRK1 and VRK2, with structural similarity to vaccinia virus B1R kinase [3].

Biological context of VRK2

• Endogenous human vacinia-related kinase 2 (VRK2) protein is present in both the nucleus and the cytosol, which is a consequence of alternative splicing of two VRK2 messages coding for proteins of 508 and 397 amino acids, respectively [4].

Anatomical context of VRK2

• The subcellular localization of vaccinia-related kinase-2 (VRK2) isoforms determines their different effect on p53 stability in tumour cell lines [4].

Enzymatic interactions of VRK2

• Both VRK2 isoforms have an identical catalytic N-terminal domain and phosphorylate p53 in vitro uniquely in Thr18 [4].

References