Vav family

VRK2 is a Ser-Thr kinase and has two isoforms, cytosolic and nuclear. The full-length VRK2 cytosolic isoform (A) inhibits MAPK signaling by a direct interaction with the corresponding JIP1 or KSR1 scaffold proteins. As a consequence, high levels of VRK2A inhibit 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.Peer Reviewe