Vaccinia-related kinase 2

VRK2 is a Ser-Thr kinase and has two isoforms, cytosolic and nuclear. The full-length VRK2 cyto-solic isoform (A) inhibits MAPK signaling by a direct interaction with the corresponding JIP1 or KSR1 scaffold proteins. As a consequence high levels of VRK2A inhibits in a dose dependent manner signals mediated by the TAK1-MKK7-JNK in response to hypoxia or interleukin, and the signal of the ERBB2-RAS-RAF-MEK-ERK pathway. Downregulation of VRK2A relieves this inhibition and allows signal transmission in response to stimuli initiated in Receptor-tyrosine kinases (RTK), such as ERBB2. Thus, in breast cancer, VRK2A and ERBB2 present an inverse correlation. VRK2 controls protein quality by regulating degradation of misfolded proteins. Mitochondrial VRK2 controls the association of Bax to mitochondrial membranes and thus modulates apoptosis. Allelic noncoding polymorphisms of the VRK2 gene have been linked to several neurological diseases.Peer Reviewe