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J. Biol. Chem., Vol. 276, Issue 5, 3709-3717, February 2, 2001
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From the Department of Integrative Biology and Pharmacology,
University of Texas Health Science Center-Houston,
Houston, Texas 77225
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 (t1/2 < 2 min) and
dependent on agonist concentration (EC50 = 2 nM). However, internalization of receptor-bound ligand
occurred slowly (t1/2 > 180 min). Incubation of
cells with SRIF also caused a rapid (t1/2 < 2 min)
increase in sst1 receptor phosphorylation in a
dose-dependent manner (EC50 = 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.
Agonist-induced Phosphorylation of Somatostatin Receptor
Subtype 1 (Sst1)
RELATIONSHIP TO DESENSITIZATION AND INTERNALIZATION*
*
This work was supported by NIDDK National Institutes of
Health Grant DK32234 and Welch Foundation Grant AU-1410.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: Dept. of Integrative
Biology and Pharmacology, University of Texas, Houston, P. O. Box
20708, Houston, TX 77225. Tel.: 713-500-7470; Fax: 713-500-7456; E-mail: Agnes.Schonbrunn@uth.tmc.edu.
Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
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