Beta-arrestin 2 Modulates the Activity of Nuclear Receptor Rar Beta2 Through Activation of Erk2 Kinase.
From: ACADIA Pharmaceuticals Inc., San Diego, CA 92121, USA. fpiu@acadia-pharm.com
Oncogene
- Publish Date: Jan 2006
- ISSN: 0950-9232
- Volume: 25
- Issue: 2
- Pages: 218-29
- Medium: Print
- Language: English
- Citation (JAMA): Piu F, Gauthier N K, Wang F, et al. Beta-arrestin 2 Modulates the Activity of Nuclear Receptor Rar Beta2 Through Activation of Erk2 Kinase.. Oncogene Jan 2006;25:218-29
Abstract
The activity of retinoid receptors activity can be regulated by various extracellular stimuli. In an effort to understand the molecular basis for this phenomenon, the role of beta-arrestins was investigated. Beta-Arrestins constitute a class of proteins involved in the internalization of agonist-activated receptors. They have also been linked to MAPK activation suggesting a direct involvement in signaling cascades. Here, we report that beta-arrestin 2 stimulates the transcriptional activation of the retinoid RAR and RXR receptors. Of all the retinoid receptors, the RAR beta2 subtype showed the strongest sensitivity to beta-arrestin 2 action. Interestingly, this event requires the presence of the MAP kinase ERK2, but not that of JNK or P38. Site-directed mutagenesis showed that Ser 22 and Leu 217 are critical residues of the RAR beta2 receptor through which beta-arrestin 2 effects are mediated. More importantly, we demonstrate that the induction of PC12 growth inhibition by Nerve Growth Factor is indeed dependent upon RAR beta2 transcriptional activation in a beta-arrestin 2- and ERK2-dependent manner.
Mesh Headings (Keywords): Amino Acid Sequence, Animals, Arrestins, Enzyme Activation, Gene Expression Regulation, Humans, JNK Mitogen-Activated Protein Kinases, Leucine, Mice, Mitogen-Activated Protein Kinase 1, Molecular Sequence Data, Mutagenesis, Site-Directed, NIH 3T3 Cells, Nerve Growth Factor, PC12 Cells, Rats, Receptors, Retinoic Acid, Sequence Homology, Amino Acid, Serine, Transcription, Genetic, Transfection, p38 Mitogen-Activated Protein Kinases
Check for Full Text / PubMed Unique Identifier (PMID): 16170358
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