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Interactions between AT1R and GRKs: the determinants for activation of signaling pathways involved in blood pressure regulation

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Abstract

The success of Angiotensin II receptor blockers, specifically Angiotensin II type 1 receptor (AT1R) antagonists as antihypertensive drug emphasizes the involvement of AT1R in Essential hypertension. The structural insights and mutational studies of Ang II-AT1R have brought about the vision to design Ang II analogs that selectively activate the pathways with beneficial and cardioprotective effects such as cell survival and hinder the deleterious effects such as hypertrophy and cell death. AT1R belongs to G-protein coupled receptors and is regulated by G-protein coupled receptor kinases (GRKs) that either uncouples Gq protein for receptor desensitization or phosphorylate C-terminus to recruit β-arrestin for internalization of the receptor. The interaction of GRKs with ligand activated AT1R induces conformational changes and signal either Gq dependent or Gq independent pathways. These interactions might explain the complex regulatory mechanisms and offer promising ideas for hypertension therapeutics. This article reviews the functional role of AT1R, organization of GRK genes and regulation of AT1R by GRKs that play significant role in desensitization and internalization of the receptors.

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The fellowship is provided by UGC with ID: 201920-19J6107081 to P.

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  1. Department cum National Centre for Human Genome Studies and Research (NCHGSR), Panjab University, Chandigarh, 160014, India

    Poonam & Shashi Chaudhary

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Conception and design: Shashi Chaudhary and Poonam. Drafting of the article: Shashi Chaudhary and Poonam. Critical revision of the article for important intellectual content: Shashi Chaudhary. Final approval of the article: Shashi Chaudhary. All authors approved the final version of the article.

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Poonam, Chaudhary, S. Interactions between AT1R and GRKs: the determinants for activation of signaling pathways involved in blood pressure regulation. Mol Biol Rep 51, 46 (2024). https://doi.org/10.1007/s11033-023-08995-0

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