| Autor: |
Van-Ham, Irit Itzhaki, Banihashemi, Behzad, Wilson, Ariel M., Jacobsen, Kirsten X., Czesak, Margaret, Albert, Paul R. |
| Předmět: |
|
| Zdroj: |
Journal of Neurochemistry; Sep2007, Vol. 102 Issue 6, p1796-1804, 9p, 1 Black and White Photograph, 1 Diagram, 4 Graphs |
| Abstrakt: |
Although they have distinct functions, the signaling of dopamine-D2 receptor short and long isoforms (D2S and D2L) is virtually identical. We compared inhibitory regulation of extracellular signal-regulated kinases (ERK1/2) in GH4 pituitary cells separately transfected with these isoforms. Activation of rat or human dopamine-D2S, muscarinic or somatostatin receptors inhibited thyrotropin-releasing hormone-induced ERK1/2 phosphorylation, while the D2L receptor failed to inhibit this response. In order to address the structural basis for the differential signaling of D2S and D2L receptors, we examined the D2L-SS mutant, in which a protein kinase C (PKC) pseudosubstrate site that is present in the D2L but not D2S receptor was converted to a consensus PKC site. In transfected GH4 cells, the D2L-SS mutant inhibited thyrotropin-releasing hormone-induced ERK1/2 phosphorylation almost as strongly as the D2S receptor. A D2S-triple mutant that eliminates PKC sites involved in D2S receptor desensitization also inhibited ERK1/2 activation. Similarly, in striatal cultures, the D2-selective agonist quinpirole inhibited potassium-stimulated ERK1/2 phosphorylation, indicating the presence of this pathway in neurons. In conclusion, the D2S and D2L receptors differ in inhibitory signaling to ERK1/2 due to specific residues in the D2L receptor alternatively spliced domain, which may account for differences in their function in vivo. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
|
Plný text