Current Hypertension Reviews

Prof. Kazuomi Kario
Jichi Medical University
School of Medicine
Tochigi
Japan

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Receptor Fragments: Intracellular Signaling and Novel Therapeutic Targets

Author(s): Julia L. Cook.

Abstract:

Many conventional GPCRs such as those associated with apelin, endothelin, prostaglandin E2, and angiotensin have also been localized to the intracellular space, principally the nucleus. These observations have involved a broad range of tissues, isolated primary cells, and cell lines and a variety of techniques including confocal microscopy, immunohistochemistry, immunocytochemistry, and western blotting. Some receptors are transported to nucleus as holoreceptors while other receptors have been shown to be cleaved with only a portion of the receptor trafficking to nucleus. Several studies from many different laboratories indicate that, depending on the cell type, the angiotensin II type 1 receptor can exist in nuclear membrane or nucleosol and that nuclear accumulation can be induced by ligand-treatment. Moreover, a population of the angiotensin receptor is cleaved in response to angiotensin II and the cytoplasmic carboxyterminal fragment trafficks to nucleus and is a potent apoptotic reagent. In this review, we discuss AT1R cleavage in light of several other receptor cleavage events which similarly produce apoptotic fragments; functionally active intracellular cleavage fragments represent novel targets for drug development.

Keywords: Angiotensin II, intracellular, intracrine, nuclear AT1 receptor, receptor cleavage, fibroblast growth factor, tyrosine, protein-coupled receptors

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Article Details

VOLUME: 8
ISSUE: 1
Year: 2012
Page: [60 - 70]
Pages: 11
DOI: 10.2174/157340212800504972