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J Biol Chem. 1997 Sep 19;272(38):23769-74.

Phosphorylation of four amino acid residues in the carboxyl terminus of the rat somatostatin receptor subtype 3 is crucial for its desensitization and internalization.

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Institut für Zellbiochemie und Klinische Neurobiologie, Universität Hamburg, 20246 Hamburg, Germany.


Agonist-dependent internalization of the rat somatostatin receptor subtype 3 (SSTR3) requires four hydroxyl amino acids (Ser341, Ser346, Ser351, and Thr357) in the receptor C terminus (Roth, A., Kreienkamp, H.-J., Nehring, R., Roostermann, D., Meyerhof, W. and Richter, D. (1997) DNA Cell Biol. 16, 111-119). Here we report on the molecular mechanism responsible for the endocytotic process by analyzing the agonist-dependent phosphorylation of wild-type and mutant receptors expressed in human embryonic kidney cells. Wild-type SSTR3 is phosphorylated in response to agonist treatment. Phosphorylation is markedly reduced in a S341A/S346A/S351A triple mutant and is also reduced, but to a lesser extent, in the T357A point mutant. Internalization of the wild-type receptor is preceded by a functional desensitization of the receptor; in contrast, the triple serine mutant does not desensitize after treatment with agonists as assayed by its ability to inhibit forskolin-stimulated adenylate cyclase activity. After internalization via a clathrin-coated vesicle mediated endocytotic pathway, SSTR3 efficiently recycles to the cell surface, suggesting that agonist mediated endocytosis is necessary for the functional resensitization of a phosphorylated and desensitized receptor.

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