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Physiological Roles for G Protein-Regulated Adenylyl Cyclase Isoforms: Insights from Knockout and Overexpression Studies
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Cyclic AMP is a universal second messenger, produced by a family of adenylyl cyclase (AC) enzymes. The last three decades have brought a wealth of new information about the regulation of cyclic AMP production by ACs. Nine hormone-sensitive, membrane-bound AC isoforms have been identified in addition to a tenth isoform that lacks membrane spans and more closely resembles the cyanobacterial AC enzymes. New model systems for purifying and characterizing the catalytic domains of AC have led to the crystal structure of these domains and the mapping of numerous interaction sites. However, big hurdles remain in unraveling the roles of individual AC isoforms and their regulation in physiological systems. In this review we explore the latest on AC knockout and overexpression studies to better understand the roles of G protein regulation of ACs in the brain, olfactory bulb, and heart.
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“Metabolism–cAMP coupling refers to the signaling cascade that occurs after the conversion of ATP, which is generated during intracellular glucose metabolism, into cAMP by adenylate cyclase (AC),53 which in turn activates protein kinase A (PKA)54 and cAMP-regulated guanine nucleotide exchange factors, also referred to as exchange protein directly activated by cAMP (Epac) 2.55, 56”
From Pancreatic regulation of glucose homeostasis. (2016) · cites this paper as [53]
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“Overall, this pattern of regulation categorizes the isoforms into four main groups. Group I consists of AC1, AC3, and AC8, which are all Ca2+ stimulated. Group II consists of Gβγ-stimulated AC2, AC4, and AC7. Group III is Gαi-inhibited and Ca2+-inhibited AC5 and AC6. Group IV contains AC9 (TABLE 1) (50).”
From Physiological roles of mammalian transmembrane adenylyl cyclase isoforms (2022) · cites this paper as [50]
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“Because of a general lack of isoform-specific inhibitors, there has been an emphasis on knockout and overexpression studies to tease out the specific roles of the isoforms in various systems and pathologies (50).”
From Physiological roles of mammalian transmembrane adenylyl cyclase isoforms (2022) · cites this paper as [50]
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Metadata
- Authors
- Sadana, R., & Dessauer, C. W.
- Affiliations
- The University of Texas Health Science Center at Houston (US)
- Venue
- Neurosignals
- Publisher
- S. Karger AG
- Published
- 2009
- Volume
- 17
- Issue
- 1
- Pages
- 5-22
- ISSN
- 1424-862X (ISSN-L)
- 1424-8638
- PMC
- PMC2790773
- OpenAlex
- W2055802786
- Cited by
- 361
- References
- 203
- Citations by year
- 2026: 10 · 2025: 20 · 2024: 20 · 2023: 16 · 2022: 23 · 2021: 32 · 2020: 21 · 2019: 17 · 2018: 22 · 2017: 21 · 2016: 15 · 2015: 18 · 2014: 24 · 2013: 28 · 2012: 25
- FWCI
- 1.26
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Neurosignals (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of General Medical Sciences (GM 60419, R01GM060419)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Phosphodiesterase function and regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- adenylyl cyclase isoforms, G protein regulation, cyclic AMP, second messenger signaling, brain, olfactory bulb, heart
- MeSH terms
- Adenylyl Cyclases, Animals, Brain, Calcium, Isoenzymes, Memory, Myocardium, Nerve Degeneration, Neuronal Plasticity, Olfactory Bulb, Pain, Protein Conformation, Apoptosis, Substance-Related Disorders, Heterotrimeric GTP-Binding Proteins
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