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Knockout of striatal enriched protein tyrosine phosphatase in mice results in increased ERK1/2 phosphorylation.

STriatal Enriched protein tyrosine Phosphatase (STEP) is a brain-specific protein that is thought to play a role in synaptic plasticity. This hypothesis is based on previous findings demonstrating a role for STEP in the regulation of the extracellular signal-regulated kinase1/2 (ERK1/2). We have now generated a STEP knockout mouse and investigated the effect of knocking out STEP in the regulation of ERK1/2 activity. Here, we show that the STEP knockout mice are viable and fertile and have no detectable cytoarchitectural abnormalities in the brain. The homozygous knockout mice lack the expression of all STEP isoforms, whereas the heterozygous mice have reduced STEP protein levels when compared with the wild-type mice. The STEP knockout mice show enhanced phosphorylation of ERK1/2 in the striatum, CA2 region of the hippocampus, as well as central and lateral nuclei of the amygdala. In addition, the cultured neurons from KO mice showed significantly higher levels of pERK1/2 following synaptic stimulation when compared with wild-type controls. These data demonstrate more conclusively the role of STEP in the regulation of ERK1/2 activity.

Pubmed ID: 18932218

Authors

  • Venkitaramani DV
  • Paul S
  • Zhang Y
  • Kurup P
  • Ding L
  • Tressler L
  • Allen M
  • Sacca R
  • Picciotto MR
  • Lombroso PJ

Journal

Synapse (New York, N.Y.)

Publication Data

January 30, 2009

Associated Grants

  • Agency: NIDA NIH HHS, Id: DA017360
  • Agency: NIMH NIH HHS, Id: K02 MH001527
  • Agency: NIMH NIH HHS, Id: K02 MH001527-10
  • Agency: NIMH NIH HHS, Id: MH01527
  • Agency: NIMH NIH HHS, Id: MH52711
  • Agency: NIDA NIH HHS, Id: R01 DA017366
  • Agency: NIDA NIH HHS, Id: R01 DA017366-05
  • Agency: NIMH NIH HHS, Id: R01 MH052711
  • Agency: NIMH NIH HHS, Id: R01 MH052711-15

Mesh Terms

  • Amygdala
  • Animals
  • Cells, Cultured
  • Corpus Striatum
  • Hippocampus
  • Mice
  • Mice, Knockout
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Phosphorylation
  • Protein Tyrosine Phosphatases, Non-Receptor
  • Up-Regulation