VRK3-mediated inactivation of ERK signaling in adult and embryonic rodent tissues.
Vaccinia-related kinase 3 (VRK3), previously characterized as a direct activator of vaccinia H1-related (VHR) phosphatase, inactivates extracellular signal-regulated kinase (ERK) in the nucleus of neuronal cells. Here we show that VRK3 is expressed in various other rodent tissues and in embryos, and regulates VHR phosphatase activity in these tissues. We observed colocalization of VRK3 and VHR in the testis tissue and could detect protein complex containing VRK3, VHR and ERK in immunoprecipitation analysis. Notably, the addition of recombinant VRK3 protein to total protein lysates, obtained either from adult tissues or embryos, enhanced the phosphatase activity of VHR, but not the activity of MKP3. The results further indicate that the VHR-VRK3 complex is a phosphatase-active form. In addition, we found that VRK3 can regulate EGF-induced cellular growth signaling that is mediated by ERK activation. Our results suggest that in addition to neuronal cells, various other rodent adult tissues and embryos possess a common signaling mechanism which is involved in an indirect regulation of ERK activity by VRK3-mediated VHR activity.
Department of Life Science, Biotechnology Research Center, Division of Molecular and Life Science, Pohang University of Science and Technology (POSTECH), San-31, Hyoja-Dong, Pohang, 790-784, Republic of Korea.
Tae-Hong
TH
Kang
Kyong-Tai
KT
Kim
D000375:Aging / Q000502:physiology*; D000818:Animals; D002460:Cell Line; D054640:Dual Specificity Phosphatase 3 / Q000378:metabolism; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D015971:Gene Expression Regulation, Enzymologic; D020935:MAP Kinase Signaling System; D008297:Male; D051379:Mice; D009928:Organ Specificity; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats
D034741:RNA, Small Interfering; D017346:Protein Serine-Threonine Kinases; C527264:VRK3 protein, rat; C475142:Vrk3 protein, mouse; D048049:Extracellular Signal-Regulated MAP Kinases; D054640:Dual Specificity Phosphatase 3; C517026:Dusp3 protein, mouse