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cAMP signalling

QuestionAnswer
De Rooij et al 1998 As known small GTPases activating Rap1 are bound and activated by calcium and DAG they looked for similar proteins with a cAMP binding site. Found Epac and showed that knocking up/down altered Rap1 activity. Epac stuck to beads binds radiolabelled cAMP
Krumins and Gilman 2006 Shows the problems of G protein knockdown, often you see compensatory upregulation of another isoform, similarly adenylyl cyclase activity may be altered to compensate. Too many mechanisms to draw strong conclusions, particularly in long term studies.
Krupinski et al 1989 Structure of AC based on DNA sequence. Protein immobilised by bound forskolin, antibody then generated, trypsin to digest purified enzyme before sequencing fragments. Seq used to make DNA primer which was used to get cDNA. Seq similar to P-glycoprotein
Cooper et al 1995 Review of ACs and their regulation by Ca. A combination of cAMP stimulated Ca entry and Ca inh of AC has the potential to create a stable oscillation in levels of both messengers. Ca source is important, intracell/extracell, may have diff effects
Masada et al 2009 ACs 1&8 are stimulated by calcium. N terminus of AC8 is needed for Ca stim, not the case for AC1. Both CaM Ca binding sites must be occupied for AC1 stim. AC1 binds CaM at its C1b domain, AC8 binds CaM at the N terminus and in the C2b domain.
Mou et al 2009 Calcium inh competes with Mg (reqd as a cofactor). Share a binding site. Calcium inh both forward and reverse reactions of the protein. Experiments used catalytic core made up of C1 from AC5 and C2 from AC2
Munro 2003 (Only author) Review of lipid rafts: Sterols and sphingolipids involved. Membrane distribution of sphingolipids altered in apoptosis, normally concentrated in outer membrane. Sphingolipids prevent membrane solidification at low temps, favour an ordered arrangement.
Hancock 2006 (only author) AFM indicates 30-80nm, domains become visible as cholesterol rises (still some contention over size). Rafts form and disperse v. quickly. Larger rafts may be endocytosed. Disruption of actin cytoskeleton disrupts lipid rafts as does cholesterol depletion.
Chen et al 2007 1st description of pathological mutation in an AKAP (namely yotiao/AKAP9), causes long QT. Normally associates with the Iks channel and allows regulation of this channel by cAMP. Found in 2% of caucasian subjects with long QT
Sadana and Dessauer 2009 Review of AC isoforms and their physiological roles. All membrane ACs activated by Gs, AC5+6 inh by Gia, AC1 only inh once overactive, no basal effect. Gby has conflicting effects depending on isoform. non-phys Ca levels compete with Mg for cofactor slot.
Yoshimura et al 1996 D1a and mu opioid receptors transfected into HEK with ACs. Dopamine stims AC5+7, opioids add to AC7 stim but reduce AC5 activity. Beta-gamma scavenger suppresed AC7 stim by morphine. May be interplay between stimulatory alpha subunit and inh By complex
Nicol et al 2007 Retinal activity refines retinotopic map. TTX had no effect on sprouting but less retraction, poor map formed. Mutant w/o exocytosis made decent map, exocyt not reqd. Removed EC Ca and blocked retraction, rescued by creating cAMP oscillations (photocage)
Dell'Acqua and Scott 1997 Review of PKA anchoring via RII/RI, vast majority of anchoring is to RII domains, leaving RI-containing type I PKA soluble.
Dodge et al 2001 Evidence that PDE and PKA are both present on an anchoring protein, disrupted interaction. PDE maintains PKA activation at a low level, while PKA activation upregulates PDE activity in a negative feedback mechanism.
Fagan et al 2000 ACs of cholesterol depleted cells are insensitive to capacitative calcium entry, restored by calcium repletion. Caveolin is able to inhibit some ACs meaning that it is regulatory as well as structural.
Huang et al 1997 αi found not to be present in morphologically evident caveolae markable with caveolin antibodies, although they also appeared in other defined regions of membrane seemingly differentiated by qualities other than the presence of caveolin. Used antibodies.
Johnson et al 1994 CaL channel binding to PKA via AKAP is required for potentiation, no effect on the basal activity, phosphorylation causes negative shift of voltage dependence and slows deactivation. Already known that they colocalised, showed that PKA regulated CaL
Jurevicius and Fischmeister 1996 Forskolin camp signal more general than beta agonist despite same proportion of the cell being exposed. Faster coupling of beta stimulation caused cAMP increase caused Ca channel opening, forskolin caused a slower response despite activating more AC.
Michel & Scott 2002 Review of AKAPs in signal transduction. 2 cAMP molecules bind each regulatory subunit causing dissociation (these reg subs are bound by AKAP). 1st AKAPs contaminated RII purifications. AKAPs invovled in RyR reg, RyR hyperphos in failing hearts.
Ostrom et al 2000 Along with Rybin 2000 showed that signalling domains exist for beta ARs and that these affect the ability of receptors to couple to their downstream signalling partners, specifically in cardiomyocytes. Caveolae are the means of localisation here.
Rybin et al 2000 Showed that B1 and 2 receptors have different sensitivity to M2 interference. B2 are in caveolae, B1 and M2 are not so B2 punch above their weight. Sucrose fractioning then immunoblot of SDS PAGE.
Sloboda et a1 1975 Binding of protein kinase to AKAPs remained stable through several rounds of microtubule association and dissociation (build up and breakdown). Nanomolar affinity.
Perry et al 2002 Agonists cause localisation of PDE to beta arrestin, this aids beta arrestin mediated homologous desensitisation and provides negative feedback.
Pike 2003 (only author) Raft review: Lipid rafts defined by low density and insolubility in 1% triton X, caveolae 100nm diameter. B2Rs leave rafts on agonist binding, BARK signalling can cause B2R to leave rafts, disconnects from signalling machinery. Rafts may aid endocytosis.
Rich et al 2001 Shows dissociation between membrane cAMP levels as measured by activation of cyclic nucleotide gated channels (against dose-response from mebrane patches - lack of scaffold?) and global cAMP measured by radiolabelling
Rosenmund et al 1994 Enhancement of AMPA/kainate currents by association with PKA and AKAP. Maintenance of PKA phosphorylation is needed for basal activity. Used a peptide fragment to reduce association.
Tasken 2001 Shows using immunofluorescence that AKAP, PDE and PKA reg subunits are found at the centrosome, presumably playing a role in microtubule organisation.
Van Deurs et al 2003 Review: Caveolae regulation of NOS
Willoughby et al 2006 Identifies gravin as the AKAP that colocalises PKA and PDE4, this aids the shut-off of the signal as PKA activates PDE4. Gravin can associate with BetaRs through beta arrestin as part of desensitisation
Wong & Scott 2004 Review - AKAPs and signalling. More than 50 AKAPs identified, bind with hydrophobic interactions. Some PDE isoforms increase AKAP affinity after PKA phosphorylation. Gravin directs PKA and PKC to the neuromuscular junction.
Malchow & Gerisch 1974 cAMP can act as an extracellular ligand for receptors in the dictyostelium slime mould. Used in chemotaxis as the cells of the slime mould become a mobile slug in response to scarcity of food. Used radiolabelled cAMP to show binding to cell.
Created by: Jonmassie