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The Striatum Enriched Tyrosine Phosphatase Regulates the Dopaminergic Neuronal Development
Author(s) -
Kim Sung Yul,
Kim Yong Nyun,
Chang Min Seok,
Lee Jong Eun,
Baik JaHyun
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.lb88
Subject(s) - dopaminergic , striatum , mapk/erk pathway , dopamine , tyrosine hydroxylase , dopaminergic pathways , dopamine receptor d2 , microbiology and biotechnology , protein tyrosine phosphatase , neuroscience , signal transduction , biology
The striatum enriched tyrosine phosphatase (STEP) is highly expressed within dopaminergic neurons in the striatum. The localization of STEP within dopaminoceptive neurons raised the possibility that STEP may interact with the dopamine receptors. In this study, we investigated the role of STEP on dopamine D2 receptors (D2R)‐mediated extracellular signal‐related kinase (ERK) signaling pathway. STEP appeared to be dephosphorylated and activated upon the stimulation of D2R. The developmental and regional expression of STEP in mouse brain announced that STEP is probably involved in the control of dopaminergic neuronal development. The treatment of oligomeric STEP siRNA (siSTEP) significantly blunted the quinpirole‐induced increase in the number of dopaminergic neurons from WT mice, while this was not detected in primary mesencephalic cultures from D2R−/− mice. Furthermore, the silencing of STEP expression perturbed D2R‐mediated ERK signaling in dopaminergic neuronal cells from WT mice, but not in D2R−/− mice. These results suggest that the regulation of ERK signaling by STEP plays a critical role in D2R‐mediated dopaminergic neuronal development. [This work was supported by basic research grant from KOSEF (Grant No. R01‐2004‐000‐10671‐0) and by a grant (Grant No. M103KV010014‐06K2201‐01410) from Brain Research Center of the 21st Century Frontier Research Program funded by the Korean Ministry of Science and Technology.]