Receptor Fragments: Intracellular Signaling and Novel Therapeutic Targets
Julia L. Cook.
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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