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Translation of striatal‐enriched protein tyrosine phosphatase (STEP) after β1‐adrenergic receptor stimulation
Author(s) -
Hu Yaer,
Zhang Yang,
Venkitaramani Deepa V.,
Lombroso Paul J.
Publication year - 2007
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2007.04749.x
Subject(s) - anisomycin , translation (biology) , pi3k/akt/mtor pathway , mapk/erk pathway , protein tyrosine phosphatase , microbiology and biotechnology , stimulation , protein kinase b , biology , ly294002 , chemistry , signal transduction , medicine , endocrinology , kinase , biochemistry , messenger rna , gene
The β‐adrenergic system is implicated in long‐term synaptic plasticity in the CNS, a process that requires protein synthesis. To identify proteins that are translated in response to β‐adrenergic receptor stimulation and the pathways that regulate this process, we investigated the effects of isoproterenol on the translation of striatal‐enriched protein tyrosine phosphatase (STEP) in both cortico‐striatal slices and primary neuronal cultures. Isoproterenol stimulation induced a rapid dose‐dependent increase in STEP expression. Anisomycin blocked the increase in STEP expression while actinomycin D had no effect, suggesting a translation‐dependent mechanism. Isoproterenol‐induced STEP translation required activation of β1‐receptors. Application of the MAPK/ERK kinase (MEK) inhibitor SL327 blocked both isoproterenol‐induced activation of pERK and subsequent STEP translation. Inhibitors of PI3K (LY294002) or mTOR (rapamycin) also completely blocked STEP translation. These results suggest that co‐activation of both the ERK and PI3K‐Akt‐mTOR pathways are required for STEP translation. As one of the substrates of STEP includes ERK itself, these results suggest that STEP is translated upon β‐adrenergic activation as part of a negative feedback mechanism.