Agonist activated adrenocorticotropin receptor internalizes via A clathrin-mediated G protein receptor kinase dependent mechanism

A. H. Baig, F. M. Swords, M. Szaszák, P. J. King, L. Hunyady, A. J L Clark

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

The physiological effects of the pituitary hormone, adrenocorticotropic hormone (ACTH) on the adrenal are mediated by the melanocortin 2 receptor (MC2R), a G protein coupled receptor (GPCR) that signals via adenylate cyclase to elevate intracellular cyclic AMP (cAMP) levels. The function and expression of the receptor is likely to be a major determinant of the response to ACTH. Following repeated stimulation, the cAMP signal is diminished or desensitized. Prolonged desensitization may involve internalization of the receptor. Internalization may occur by at least two mechanisms - receptor mediated endocytosis via clathrin-coated pits and by caveolae mediated internalization. The mode of internalization for the endogenous MC2R in Y1 cells was determined using radiolabelled ACTH. Treatment of Y1 cells with hypertonic sucrose or with concanavalin A, which inhibit clathrin-mediated endocytosis, blocked internalization. Filipin and nystatin, which inhibit caveolae formation, did not influence internalization. A dominant negative GRK2 inhibited internalization whilst the protein kinase A (PKA) consensus site mutant MC2R (S208A) internalized normally. However, dominant negative V53D β-arrestin-1 did not inhibit ACTH internalization in Y1 cells. In conclusion, it appears that the MC2R in Y1 cells internalizes by a G protein coupled receptor kinase (GRK) dependent clathrin-coated pit mechanism.

Original languageEnglish
Pages (from-to)281-289
Number of pages9
JournalEndocrine Research
Volume28
Issue number4
DOIs
Publication statusPublished - 2002

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Receptor, Melanocortin, Type 2
Cyclic GMP-Dependent Protein Kinases
Clathrin
Adrenocorticotropic Hormone
Caveolae
Endocytosis
Cyclic AMP
G-Protein-Coupled Receptor Kinases
Filipin
Arrestin
Nystatin
Pituitary Hormones
Concanavalin A
G-Protein-Coupled Receptors
Cyclic AMP-Dependent Protein Kinases
Adenylyl Cyclases
Sucrose

ASJC Scopus subject areas

  • Endocrinology

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Agonist activated adrenocorticotropin receptor internalizes via A clathrin-mediated G protein receptor kinase dependent mechanism. / Baig, A. H.; Swords, F. M.; Szaszák, M.; King, P. J.; Hunyady, L.; Clark, A. J L.

In: Endocrine Research, Vol. 28, No. 4, 2002, p. 281-289.

Research output: Contribution to journalArticle

Baig, A. H. ; Swords, F. M. ; Szaszák, M. ; King, P. J. ; Hunyady, L. ; Clark, A. J L. / Agonist activated adrenocorticotropin receptor internalizes via A clathrin-mediated G protein receptor kinase dependent mechanism. In: Endocrine Research. 2002 ; Vol. 28, No. 4. pp. 281-289.
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