ArticleBiochimica et biophysica acta2008
Agonist-dependent internalization and trafficking of the human prostacyclin receptor: a direct role for Rab5a GTPase.
Article in Biochimica et biophysica acta, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 24 citations in OpenAlex.
- Sustained CREB Phosphorylation Is Associated with Neuritogenic Prostanoid Signaling in NSC-34 Cells.Cells · 2026Article
- A Review of Prostanoid Receptors: Expression, Characterization, Regulation, and Mechanism of Action.Journal of cell communication and signaling · 2021Review
- L-type prostaglandin D synthase regulates the trafficking of the PGDThe Journal of biological chemistry · 2019Article
- The α-arrestin ARRDC3 mediates ALIX ubiquitination and G protein-coupled receptor lysosomal sorting.Molecular biology of the cell · 2015Article
- Regulation of the human prostacyclin receptor gene by the cholesterol-responsive SREBP1.Journal of lipid research · 2012Article
- Regulation of β2-adrenergic receptor maturation and anterograde trafficking by an interaction with Rab geranylgeranyltransferase: modulation of Rab geranylgeranylation by the receptor.The Journal of biological chemistry · 2011Article
- Prostacyclin receptor regulation--from transcription to trafficking.Current molecular medicine · 2011Review
- Interaction of the human prostacyclin receptor with the PDZ adapter protein PDZK1: role in endothelial cell migration and angiogenesis.Molecular biology of the cell · 2011Article
- The role of Rab5a GTPase in endocytosis and post-endocytic trafficking of the hCG-human luteinizing hormone receptor complex.Cellular and molecular life sciences : CMLS · 2011Article
- Comprehensive biochemical analysis of rare prostacyclin receptor variants: study of association of signaling with coronary artery obstruction.The Journal of biological chemistry · 2011Article
- Interaction of the human prostacyclin receptor with Rab11: characterization of a novel Rab11 binding domain within alpha-helix 8 that is regulated by palmitoylation.The Journal of biological chemistry · 2010Article
- Immature and mature species of the human Prostacyclin Receptor are ubiquitinated and targeted to the 26S proteasomal or lysosomal degradation pathways, respectively.Journal of molecular signaling · 2009Article
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Authors and funding
3 authors at 1 institution in 1 country.
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Abstract
The human prostacyclin receptor (hIP) undergoes rapid agonist-induced internalization by largely unknown mechanism(s). Herein the involvement of Rab5 in regulating cicaprost-induced internalization of the hIP expressed in human embryonic kidney 293 cells was investigated. Over-expression of Rab5a significantly increased agonist-induced hIP internalization. Additionally, the hIP co-localized to Rab5a-containing endocytic vesicles in response to cicaprost stimulation and there was a coincident net translocation of Rab5 from the cytosol/soluble fraction of the cell. Co-immunoprecipitation studies confirmed a direct physical interaction between the hIP and Rab5a that was augmented by cicaprost. Whilst the dominant negative Rab5a(S34N) did not show decreased interaction with the hIP or fully impair internalization, it prevented hIP sorting to endocytic vesicles. Moreover, the GTPase deficient Rab5a(Q79L) significantly increased internalization and co-localized with the hIP in enlarged endocytic vesicles. While deletion of the carboxyl terminal (C)-tail domain of the hIP did not inhibit agonist-induced internalization, co-localization or co-immunoprecipitation with Rab5a per se, receptor trafficking was altered suggesting that it contains structural determinant(s) for hIP sorting post Rab5-mediated endocytosis. Taken together, data herein and in endothelial EA.hy 926 cells demonstrate a direct role for Rab5a in agonist-internalization and trafficking of the hIP and increases knowledge of the factors regulating prostacyclin signaling.
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