| First Author | Guiramand J | Year | 1995 |
| Journal | J Biol Chem | Volume | 270 |
| Issue | 13 | Pages | 7354-8 |
| PubMed ID | 7706278 | Mgi Jnum | J:41193 |
| Mgi Id | MGI:893272 | Doi | 10.1074/jbc.270.13.7354 |
| Citation | Guiramand J, et al. (1995) Alternative splicing of the dopamine D2 receptor directs specificity of coupling to G-proteins. J Biol Chem 270(13):7354-8 |
| abstractText | Two isoforms of the dopamine D2 receptor have been characterized, D2L (long) and D2S (short), generated by alternative splicing from the same gene. They differ by an in-frame insert of 29 amino acids specific to D2L within the putative third intracytoplasmic loop of the receptor. We have previously demonstrated (Montmayeur, J.-P., Guiramand, J., and Borelli, E. (1993) Mol. Endocrinol. 7, 161-170) that D2S and D2L, although presenting very similar pharmacological profiles, couple differently to the alpha-subunit of guanine nucleotide-binding regulatory proteins (G-proteins). In particular, D2L, but not D2S, requires the presence of the alpha-subunit of the inhibitory G-protein (G alpha i2) to elicit greater inhibition of adenylyl cyclase activity. The insert present in D2L must therefore confer the specificity of interaction with G alpha i2. Thus, we introduced substitution mutations within the D2L insert. These mutant receptors were expressed in JEG3 cells, a G alpha i2-deficient cell line, scoring for those presenting an increased inhibition of adenylyl cyclase by dopamine. Our analysis identified two mutants, S259/262A and D249V, with these properties. These results clearly show that the insert present in D2L plays a critical role in the selectivity for the G-proteins interacting with the receptor. |
