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PMID:18035061

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Citation

Kang, TH and Kim, KT (2008) VRK3-mediated inactivation of ERK signaling in adult and embryonic rodent tissues. Biochim. Biophys. Acta 1783:49-58

Abstract

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.

Links

PubMed Online version:10.1016/j.bbamcr.2007.10.011

Keywords

Aging/physiology; Animals; Cell Line; Dual Specificity Phosphatase 3/metabolism; Enzyme Activation; Extracellular Signal-Regulated MAP Kinases/genetics; Extracellular Signal-Regulated MAP Kinases/metabolism; Gene Expression Regulation, Developmental; Gene Expression Regulation, Enzymologic; MAP Kinase Signaling System; Male; Mice; Organ Specificity; Protein Binding; Protein-Serine-Threonine Kinases/genetics; Protein-Serine-Threonine Kinases/metabolism; RNA, Small Interfering/genetics; Rats

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

RAT:A0A0G2K3I9

involved_in

GO:0001701: in utero embryonic development

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:G3V9L3

involved_in

GO:0001701: in utero embryonic development

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:VRK3

enables

GO:0019903: protein phosphatase binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:Q9D7X3

F

Seeded From UniProt

complete

MOUSE:VRK3

acts_upstream_of_or_within

GO:0032516: positive regulation of phosphoprotein phosphatase activity

ECO:0000353: physical interaction evidence used in manual assertion

PR:Q9D7X3

P

Seeded From UniProt

complete

MOUSE:VRK3

acts_upstream_of_or_within

GO:0070373: negative regulation of ERK1 and ERK2 cascade

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:DUS3

acts_upstream_of_or_within

GO:0006470: protein dephosphorylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:DUS3

enables

GO:0004721: phosphoprotein phosphatase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete


See also

References

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