Biological roles of cAMP: variations on a theme in the different kingdoms of life DOI

Juana M. Gancedo

Biological reviews/Biological reviews of the Cambridge Philosophical Society, Journal Year: 2013, Volume and Issue: 88(3), P. 645 - 668

Published: Jan. 29, 2013

Abstract Cyclic AMP ( cAMP ) plays a key regulatory role in most types of cells; however, the pathways controlled by may present important differences between organisms and tissues within specific organism. Changes levels are caused multiple triggers, affecting adenylyl cyclases, enzymes that synthesize . Adenylyl cyclases form large diverse family including soluble forms others with one or more transmembrane domains. Regulatory mechanisms for involve either interaction proteins, as happens Escherichia coli yeasts, calcium bicarbonate ions, occurs mammalian cells. The can be regulated variety among which α subunit βγ complex from G proteins coupled to membrane receptors prominent. also activity phosphodiesterases, hydrolyze Phosphodiesterases , cGMP calcium‐calmodulin phosphorylation different protein kinases. Regulation through depends on its binding proximal targets, this turn causing changes distal targets. Specifically, subunits ‐dependent kinases PKAs affects substrates PKA exchange directly activated Epac regulates small GTPases transcription factors such receptor CRP virulence factor regulator Vfr modifies rate certain genes, while ion channels modulates their directly. Further studies signalling will have implications, not only advancing fundamental knowledge but identifying targets development new therapeutic agents.

Language: Английский

Principles of c-di-GMP signalling in bacteria DOI
Regine Hengge

Nature Reviews Microbiology, Journal Year: 2009, Volume and Issue: 7(4), P. 263 - 273

Published: March 16, 2009

Language: Английский

Citations

1451

A Coupled SYSTEM of Intracellular Ca 2+ Clocks and Surface Membrane Voltage Clocks Controls the Timekeeping Mechanism of the Heart’s Pacemaker DOI Open Access
Edward G. Lakatta, Victor A. Maltsev, Tatiana M. Vinogradova

et al.

Circulation Research, Journal Year: 2010, Volume and Issue: 106(4), P. 659 - 673

Published: March 4, 2010

Abstract: Ion channels on the surface membrane of sinoatrial nodal pacemaker cells (SANCs) are proximal cause an action potential. Each individual channel type has been thoroughly characterized under voltage clamp, and ensemble ion currents reconstructed in silico generates rhythmic potentials. Thus, this can be envisioned as a “membrane clock” (M clock). Localized subsarcolemmal Ca 2+ releases generated by sarcoplasmic reticulum via ryanodine receptors during late diastolic depolarization referred to intracellular “Ca clock,” because their spontaneous occurrence is periodic clamp or detergent-permeabilized SANCs, well. In spontaneously firing M clocks do not operate isolation but work together numerous interactions modulated voltage, , protein kinase A CaMKII-dependent phosphorylation. Through these interactions, 2 subsystem become mutually entrained form robust, stable, coupled-clock system that drives normal cardiac cell automaticity. G protein–coupled signaling creates flexibility, ie, effects changes potential rate, impacting very same factors regulate robust basal function. This review examines evidence forms basis concept SANCs.

Language: Английский

Citations

595

Caveolae as Organizers of Pharmacologically Relevant Signal Transduction Molecules DOI
Hemal H. Patel, Fiona Murray, Paul A. Insel

et al.

The Annual Review of Pharmacology and Toxicology, Journal Year: 2007, Volume and Issue: 48(1), P. 359 - 391

Published: Oct. 3, 2007

Caveolae, a subset of membrane (lipid) rafts, are flask-like invaginations the plasma that contain caveolin proteins, which serve as organizing centers for cellular signal transduction. Caveolins (-1, -2, and -3) have cytoplasmic N C termini, palmitolylation sites, scaffolding domain facilitates interaction organization signaling molecules so to help provide coordinated efficient Such components include upstream entities (e.g., G protein-coupled receptors (GPCRs), receptor tyrosine kinases, steroid hormone receptors) downstream heterotrimeric low-molecular-weight effector enzymes, ion channels). Diseases associated with aberrant may result in altered localization or expression proteins caveolae. Caveolin-knockout mice numerous abnormalities, some reflect impact total body knockout throughout life span. This review provides general overview caveolins caveolae, localize role caveolae/caveolin cardiac pulmonary pathophysiology, pharmacologic implications caveolar molecules, possibility caveolae might therapeutic target.

Language: Английский

Citations

427

Underpinning compartmentalised cAMP signalling through targeted cAMP breakdown DOI
Miles D. Houslay

Trends in Biochemical Sciences, Journal Year: 2009, Volume and Issue: 35(2), P. 91 - 100

Published: Oct. 27, 2009

Language: Английский

Citations

418

Physiological Roles for G Protein-Regulated Adenylyl Cyclase Isoforms: Insights from Knockout and Overexpression Studies DOI Open Access
Rachna Sadana, Carmen Dessauer

Neurosignals, Journal Year: 2008, Volume and Issue: 17(1), P. 5 - 22

Published: Oct. 27, 2008

Cyclic AMP is a universal second messenger, produced by family of adenylyl cyclase (AC) enzymes. The last three decades have brought wealth new information about the regulation cyclic production ACs. Nine hormone-sensitive, membrane-bound AC isoforms been identified in addition to tenth isoform that lacks membrane spans and more closely resembles cyanobacterial New model systems for purifying characterizing catalytic domains led crystal structure these mapping numerous interaction sites. However, big hurdles remain unraveling roles individual their physiological systems. In this review we explore latest on knockout overexpression studies better understand G protein ACs brain, olfactory bulb, heart.

Language: Английский

Citations

357

Molecular Mechanism of Pancreatic and Salivary Gland Fluid and HCO3Secretion DOI
Min Goo Lee, Ehud Ohana, Hyun Woo Park

et al.

Physiological Reviews, Journal Year: 2012, Volume and Issue: 92(1), P. 39 - 74

Published: Jan. 1, 2012

Fluid and HCO 3 − secretion is a vital function of all epithelia required for the survival tissue. Aberrant fluid associated with many epithelial diseases, such as cystic fibrosis, pancreatitis, Sjögren's syndrome, other inflammatory autoimmune diseases. Significant progress has been made over last 20 years in our understanding secretion, particular by secretory glands. glands two-step process. Acinar cells secrete isotonic which major salt NaCl. Subsequently, duct modifies volume electrolyte composition to absorb Cl . The relative secreted acinar modification fluids varies among meet their physiological functions. In pancreas, small amount NaCl-rich fluid, while absorbs secretes bulk pancreatic juice. appears be driven active secretion. salivary glands, saliva that contains high concentrations Na + both K this review, we focus on molecular mechanism pancreas highlight similarities fundamental mechanisms cell functions, point out differences gland-specific secretions.

Language: Английский

Citations

343

Store-operated CRAC channels: function in health and disease DOI

Anant B. Parekh

Nature Reviews Drug Discovery, Journal Year: 2010, Volume and Issue: 9(5), P. 399 - 410

Published: April 16, 2010

Language: Английский

Citations

311

IP3 Receptors: Toward Understanding Their Activation DOI Open Access
Colin W. Taylor,

Stephen C. Tovey

Cold Spring Harbor Perspectives in Biology, Journal Year: 2010, Volume and Issue: 2(12), P. a004010 - a004010

Published: Oct. 27, 2010

Colin W. Taylor and Stephen C. Tovey Department of Pharmacology, University Cambridge, Tennis Court Road, CB2 1PD, United Kingdom Correspondence: cwt1000{at}cam.ac.uk

Language: Английский

Citations

278

Phase Separation of a PKA Regulatory Subunit Controls cAMP Compartmentation and Oncogenic Signaling DOI Creative Commons
Jason Z. Zhang, Tsan-Wen Lu, Lucas M. Stolerman

et al.

Cell, Journal Year: 2020, Volume and Issue: 182(6), P. 1531 - 1544.e15

Published: Aug. 25, 2020

Language: Английский

Citations

259

The Prostanoid EP4 Receptor and Its Signaling Pathway DOI
Utako Yokoyama,

Kousaku Iwatsubo,

Masanari Umemura

et al.

Pharmacological Reviews, Journal Year: 2013, Volume and Issue: 65(3), P. 1010 - 1052

Published: June 17, 2013

The EP4 prostanoid receptor is one of four subtypes for prostaglandin E2. It belongs to the family G protein–coupled receptors. was originally identified, similar EP2 as a Gsα-coupled, adenylyl cyclase–stimulating receptor. signaling plays variety roles through cAMP effectors, i.e., protein kinase A and exchange activated by cAMP. However, emerging evidence from studies using pharmacological approaches genetically modified mice suggests that EP4, unlike EP2, can also be coupled Giα, phosphatidylinositol 3-kinase, β-arrestin, or β-catenin. These pathways constitute unique widely distributed in body thus various physiologic pathophysiologic roles. In particular, closely related carcinogenesis, cardiac hypertrophy, vasodilation, vascular remodeling, bone gastrointestinal homeostasis, renal function, female reproductive function. addition classic anti-inflammatory action on mononuclear cells T cells, recent has shown contributes proinflammatory well. aim this review present current findings biologic functions we will discuss its diversity standpoint EP4-mediated signaling.

Language: Английский

Citations

247