title: Translation of striatal-enriched protein tyrosine phosphatase (STEP) after beta1-adrenergic receptor stimulation.
abstract: The beta-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 beta-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 beta1-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 beta-adrenergic activation as part of a negative feedback mechanism.
authors.affiliation: Child Study Center, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
authors.forename: Yaer
authors.initials: Y
authors.lastname: Hu
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.forename: Deepa V
authors.initials: DV
authors.lastname: Venkitaramani
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Lombroso
mesh_terms: D058646:Adrenergic alpha-1 Receptor Agonists; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005455:Fluorescent Antibody Technique; D007150:Immunohistochemistry; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000096:biosynthesis; D048052:Mitogen-Activated Protein Kinase 3 / Q000096:biosynthesis; D009473:Neuronal Plasticity / Q000187:drug effects; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D014176:Protein Biosynthesis / Q000187:drug effects; D011494:Protein Kinases / Q000096:biosynthesis / Q000235:genetics; D054558:Protein Tyrosine Phosphatases, Non-Receptor / Q000096:biosynthesis* / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D058646:Adrenergic alpha-1 Receptor Agonists; D000318:Adrenergic beta-Agonists; D007545:Isoproterenol; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D019869:Phosphatidylinositol 3-Kinases; D011494:Protein Kinases; D054558:Protein Tyrosine Phosphatases, Non-Receptor; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; C546845:mTOR protein, rat; C489931:Ptpn5 protein, rat