Functional coupling of a mammalian somatostatin receptor to the yeast pheromone response pathway
Functional coupling of a mammalian somatostatin receptor to the yeast pheromone response pathway
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哺乳动物生长抑素受体与酵母信息素反应途径的功能耦合
DOI:
--
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发表时间:
1995
影响因子:
5.3
通讯作者:
M. Pausch
中科院分区:
文献类型:
--
作者:
L. A. Price;E. M. Kajkowski;J. Hadcock;B. Ozenberger;M. Pausch
A detailed analysis of structural and functional aspects of G-protein-coupled receptors, as well as discovery of novel pharmacophores that exert their effects on members of this class of receptors, will be facilitated by development of a yeast-based bioassay. To that end, yeast strains that functionally express the rat somatostatin receptor subtype 2 (SSTR2) were constructed. High-affinity binding sites for somatostatin ([125I-Tyr-11]S-14) comparable to those in native tissues were detected in yeast membrane extracts at levels equivalent to the alpha-mating pheromone receptor (Ste2p). Somatostatin-dependent growth of strains modified by deletion of genes encoding components of the pheromone response pathway was detected through induction of a pheromone-responsive HIS3 reporter gene, enabling cells to grow on medium lacking histidine. Dose-dependent growth responses to S-14 and related SSTR2 subtype-selective agonists that were proportional to the affinity of the ligands for SSTR2 were observed. The growth response required SSTR2, G alpha proteins, and an intact signal transduction pathway. The sensitivity of the bioassay was affected by intracellular levels of the G alpha protein. A mutation in the SST2 gene, which confers supersensitivity to pheromone, was found to significantly enhance the growth response to S-14. In sst2 delta cells, SSTR2 functionally interacted with both a chimeric yeast/mammalian G alpha protein and the yeast G alpha protein, Gpa1p; to promote growth. These yeast strains should serve as a useful in vivo reconstitution system for examination of molecular interactions of the G-protein-coupled receptors and G proteins.
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影响因子:
56.9
作者:
KING, K;DOHLMAN, HG;LEFKOWITZ, RJ
通讯作者:
LEFKOWITZ, RJ
DOI:
--
发表时间:
1989
期刊:
The Journal of pharmacology and experimental therapeutics
影响因子:
--
作者:
Raynor,K;Reisine,T
通讯作者:
Reisine,T
DOI:
--
发表时间:
1992-10
期刊:
The Journal of biological chemistry
影响因子:
--
作者:
K. Yasuda;S. Rens‐Domiano;C. Breder;S. Law;C. Saper;T. Reisine;G. Bell
通讯作者:
K. Yasuda;S. Rens‐Domiano;C. Breder;S. Law;C. Saper;T. Reisine;G. Bell
DOI:
10.1073/pnas.79.22.6971
发表时间:
1982-01-01
期刊:
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子:
--
作者:
JOHNSTON, SA;HOPPER, JE
通讯作者:
HOPPER, JE
DOI:
--
发表时间:
1994-04
期刊:
The Journal of biological chemistry
影响因子:
--
作者:
C. Hou;R. L. Gilbert;D. Barber
通讯作者:
C. Hou;R. L. Gilbert;D. Barber