Julia L. Cook Pages 60 - 70 ( 11 )
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.
Angiotensin II, intracellular, intracrine, nuclear AT1 receptor, receptor cleavage, fibroblast growth factor, tyrosine, protein-coupled receptors
Laboratory of Molecular Genetics, Ochsner Clinic Foundation, Biomedical Research Building, 1514 Jefferson Highway, New Orleans, LA 70121, USA.