PMID: 11331411May 2, 2001Paper

Protein kinase C-mediated down-regulation of beta(2)-adrenergic receptor and gene expression in rat C6 glioma cells

Journal of Neurochemistry
M LeavittP H Fishman

Abstract

We investigated the regulation of beta(2)-adrenergic receptors (beta(2)AR) by protein kinase C (PKC) in rat C6 glioma cells at the levels of receptor activity, protein expression and gene expression. Cells exposed to 4beta-phorbol-12-myristate-13-acetate (PMA), a potent activator of PKC, exhibited a time- and concentration-dependent decrease in beta(2)AR binding activity. Maximum down-regulation was approximately 50% by 24 h and western blot analysis revealed a parallel decrease in beta(2)AR protein. In addition, PMA treatment resulted in an acute desensitization of beta(2)AR-stimulated cyclic AMP response prior to any reduction in receptor levels. PMA exposure also affected steady-state beta(2)AR mRNA levels in a time-dependent, biphasic manner. During the first 4 h, levels decreased by approximately 60% and then slowly recovered to approximately 75% of control by 24 h. As the reduction in receptor mRNA was not due to a decrease in its stability, we examined beta(2)AR gene transcription by nuclear run-on assays. Transcriptional activity in nuclei from C6 cells treated with PMA for 2 h was reduced by 70% compared to controls. Thus PKC can regulate beta(2)AR at least two levels: the first being an acute desensitization of recept...Continue Reading

References

Apr 29, 1987·Biochemical and Biophysical Research Communications·P H FishmanJ Patel
Jul 1, 1984·Proceedings of the National Academy of Sciences of the United States of America·D J KelleherG L Johnson
Jun 29, 1984·Biochemical and Biophysical Research Communications·D R SibleyR J Lefkowitz
May 5, 1995·The Journal of Biological Chemistry·B FèveA D Strosberg
Jan 1, 1993·Journal of Neurochemistry·J R Hadcock, C C Malbon
Jan 1, 1996·Journal of Receptor and Signal Transduction Research·M D Pak, P H Fishman

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Citations

Mar 24, 2005·Neuroimmunomodulation·Alicia Juana KlechaGraciela Alicia Cremaschi
Aug 15, 2008·Journal of Receptor and Signal Transduction Research·Christophe ChauveauOdile Broux

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