Abstract
All adrenergic receptors (ARs) are members of the G protein-coupled receptor superfamily and have been assumed to initiate signals primarily by activation of heterotrimeric G proteins. The three major AR families (α1, α2, β) each contain three subtypes, with all receptors within a subfamily acting through the same G proteins to initiate the same signals. α1-ARs activate Gq/11 to increase Ca2+, α2-ARs activate Gi/o to decrease cyclic adenosine 5′-monophosphate, and β-ARs activate Gs to increase cyclic adenosine 5′-monophosphate. This raises questions regarding how apparently redundant receptor subtypes have survived evolutionarily and continue to mediate distinct functions in all known higher organisms. Although the primary importance of G proteins in signaling is not in doubt, it is increasingly clear that understanding AR signaling requires additional complexity. ARs have now been shown also to interact directly with other proteins, which may be important in signaling. One class includes other G protein-coupled receptors, and increasing reports of receptor heterodimerization are transforming our view of these receptors as solitary cellular sentinels for detecting incoming signals. Another class is adaptor or scaffolding proteins responsible for local organization of specific signaling complexes, for which proximity of effector molecules may result in increased or unexpected responses. Other proteins, such as regulators of G protein signaling, may affect the specificity or extent of G protein activation. Finally, internalization of receptors may be required for certain responses, which may be independent of G protein signaling. Thus, the traditional view of a linear signaling cascade of ligand/receptor/G protein/second messenger activation is turning into a much more complex, combinatorial, and context-dependent view of AR signaling.
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© 2006 Humana Press Inc., Totowa, NJ
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Minneman, K.P. (2006). New Signal Transduction Paradigms. In: Perez, D.M. (eds) The Adrenergic Receptors. The Receptors. Humana Press. https://doi.org/10.1385/1-59259-931-1:087
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DOI: https://doi.org/10.1385/1-59259-931-1:087
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