Deepa V. Venkitaramani and Surojit Paul contributed equally to this work.
Knockout of STriatal enriched protein tyrosine phosphatase in mice results in increased ERK1/2 phosphorylation
Article first published online: 17 OCT 2008
Copyright © 2008 Wiley-Liss, Inc.
Volume 63, Issue 1, pages 69–81, January 2009
How to Cite
Venkitaramani, D. V., Paul, S., Zhang, Y., Kurup, P., Ding, L., Tressler, L., Allen, M., Sacca, R., Picciotto, M. R. and Lombroso, P. J. (2009), Knockout of STriatal enriched protein tyrosine phosphatase in mice results in increased ERK1/2 phosphorylation. Synapse, 63: 69–81. doi: 10.1002/syn.20608
- Issue published online: 17 OCT 2008
- Article first published online: 17 OCT 2008
- Manuscript Accepted: 15 AUG 2008
- Manuscript Received: 30 APR 2008
- NIH. Grant Numbers: MH01527, MH52711, DA017360
- The National Association of Research on Schizophrenia and Depression (NARSAD)
- Brown-Coxe fellowship
- tyrosine phosphatase;
- synaptic plasticity;
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. Synapse 63:69–81, 2009. © 2008 Wiley-Liss, Inc.