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Agonist-induced Phosphorylation of Somatostatin Receptor Subtype 1 (Sst1)

Authors :
Qisheng Liu
Agnes Schonbrunn
Source :
Journal of Biological Chemistry. 276:3709-3717
Publication Year :
2001
Publisher :
Elsevier BV, 2001.

Abstract

The sst1 somatostatin (SRIF) receptor subtype is widely expressed in the endocrine, gastrointestinal, and neuronal systems as well as in hormone-sensitive tumors, yet little is known about its regulation. Here we investigated the desensitization, internalization, and phosphorylation of sst1 expressed in CHO-K1 cells. Treatment of cells with 100 nm SRIF for 30 min reduced maximal SRIF inhibition of adenylyl cyclase from 40 to 10%. This desensitization was rapid (t(12) 180 min). Incubation of cells with SRIF also caused a rapid (t(12) < 2 min) increase in sst1 receptor phosphorylation in a dose-dependent manner (EC(50) = 1.3 nm), as determined in a mobility shift phosphorylation assay. Receptor phosphorylation was not affected by pertussis toxin, indicating a requirement for receptor occupancy rather than signaling. The protein kinase C activator, phorbol 12-myristate 13-acetate also stimulated sst1 receptor phosphorylation whereas forskolin did not. Both agonist- and phorbol 12-myristate 13-acetate-stimulated receptor phosphorylation occurred mainly on serine. These studies are the first to demonstrate phosphorylation of the sst1 receptor and suggest that phosphorylation mediated uncoupling, rather than sequestration, leads to its desensitization.

Details

ISSN :
00219258
Volume :
276
Database :
OpenAIRE
Journal :
Journal of Biological Chemistry
Accession number :
edsair.doi...........ef9310f1709d051dbcdecdc4eaf32eb4
Full Text :
https://doi.org/10.1074/jbc.m008873200