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• W1515033204 abstract "Chronic stimulation of brain neurons by angiotensin II (Ang II) results in a increase in norepinephrine (NE) uptake. This involves stimulation of transcription of NE transporter and tyrosine hydroxylase genes and is associated with translocation of signaling molecules and transcription factors from the cytoplasmic compartment into the neuronal nucleus (Lu et al., 1996a). We report here that the phosphorylation of p62, a glycoprotein nucleoporin of the nuclear pore complex (NPC), by MAP kinase is involved in this process. Ang II caused a time-dependent translocation of signal transducers and activators of transcription (STAT3) from the cytoplasmic compartment into the nucleus. This translocation was attenuated by pretreatment with antisense oligonucleotide (AON) to MAP kinase. Ang II also stimulated phosphorylation of p62, and a maximal phosphorylation of 12-fold was observed with 100 n m Ang II. This stimulation was blocked by losartan, an AT 1 receptor subtype-specific antagonist. The conclusion that MAP kinase is involved in Ang II-induced phosphorylation of p62 and nuclear translocation of STAT3 is supported by the following. (1) p62 phosphorylation was blocked by a peptide that competes with p62 as a MAP kinase substrate both in vitro and in vivo ; (2) AON to MAP kinase attenuated Ang II stimulation of p62 phosphorylation; and (3) in addition, it also blocked nuclear translocation of STAT3. Intracellular loading of the peptide containing MAP kinase substrate consensus of the p62 reduced Ang II stimulation of p62 phosphorylation and nuclear translocation of STAT3 in both in vivo and in vitro experiments. These observations suggest that Ang II-induced phosphorylation of p62 may accelerate the activity of the NPC, which would result in an increase in the nuclear transport of transcription factors and signaling molecules. This will stimulate transcriptional processes associated with Ang II regulation of NE neuromodulation." @default.
• W1515033204 created "2016-06-24" @default.
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• W1515033204 creator A5068719920 @default.
• W1515033204 creator A5071839746 @default.
• W1515033204 date "1998-02-15" @default.
• W1515033204 modified "2023-10-16" @default.
• W1515033204 title "Involvement of p62 Nucleoporin in Angiotensin II-Induced Nuclear Translocation of STAT3 in Brain Neurons" @default.
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• W1515033204 doi "https://doi.org/10.1523/jneurosci.18-04-01329.1998" @default.
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