Identification of the invariant chain (CD74) as an angiotensin AGTR1-interacting protein

Márta Szaszák, Hung Dar Chen, Hao Chia Chen, Albert Baukal, L. Hunyady, Kevin J. Catt

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Little is known about the protein-protein interactions that regulate the trafficking of the angiotensin II type I receptor (AGTR1) through the biosynthetic pathway. The membrane-proximal region of the cytoplasmic tail of the AGTR1 has been identified by site-directed mutagenesis studies as an essential site for normal AGTR1 folding and surface expression. Based on yeast two-hybrid screening of a human kidney cDNA library with the AGTR1 carboxyl-terminal tail as a bait, we identified the invariant chain (CD74) as a novel interacting protein. This association was confirmed by co-immunoprecipitation and co-localization studies. The binding site for CD74 on the AGTR1 carboxyl-terminal tail was localized to a site previously identified as important for the exit of the AGTR1 from the endoplasmic reticulum (ER), and conserved in many G protein-coupled receptors. Transient co-expression of CD74 with the AGTR1 in CHO-K1 cells consistently reduced the AGTR1 density at the cell surface. Furthermore, the interaction of CD74 with the carboxyl-terminal tail of the AGTP1 caused its retention in the ER and promoted its proteasomal degradation. These observations indicate that CD74 and the AGTR1 become associated in the early biosynthetic pathway, and that CD74 is a negative regulator of AGTR1 expression.

Original languageEnglish
Pages (from-to)165-176
Number of pages12
JournalJournal of Endocrinology
Volume199
Issue number2
DOIs
Publication statusPublished - Nov 2008

Fingerprint

Angiotensins
Tail
Biosynthetic Pathways
Endoplasmic Reticulum
Proteins
Angiotensin I
Angiotensin Receptors
CHO Cells
G-Protein-Coupled Receptors
Site-Directed Mutagenesis
Gene Library
Immunoprecipitation
Cell Count
Yeasts
Binding Sites
Kidney
Membranes
invariant chain

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Identification of the invariant chain (CD74) as an angiotensin AGTR1-interacting protein. / Szaszák, Márta; Chen, Hung Dar; Chen, Hao Chia; Baukal, Albert; Hunyady, L.; Catt, Kevin J.

In: Journal of Endocrinology, Vol. 199, No. 2, 11.2008, p. 165-176.

Research output: Contribution to journalArticle

Szaszák, Márta ; Chen, Hung Dar ; Chen, Hao Chia ; Baukal, Albert ; Hunyady, L. ; Catt, Kevin J. / Identification of the invariant chain (CD74) as an angiotensin AGTR1-interacting protein. In: Journal of Endocrinology. 2008 ; Vol. 199, No. 2. pp. 165-176.
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