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9 terms

Signalling by cAMP

Things I want to remember for this lecture series
STUDY
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Krupunski et al. 1989
Affinity chromatography to define the first AC.
ACI and ACVIII
Stimulated by Ca2+
ACV and ACVI
Inhibited by Ca2+
Hancock et al. 2006
Evidence for lipid rafts! Proposes a new theory for lipid rafts.
Macdougall et al. 2009
Propose new model for Ca2+ activation of AC8.

Prebound CaM to N-terminal CaMBD of even in absence of Ca2+.

Proposes that N-terminus and C-terminus CaMBD actually interact.
Rolipram
An anti-inflammatory drug that inhibits PDE IV.
Zaccolo et al. 2002
First visualisation of microdomains!!!!!

FRET based assay. Chromophore tagged catalytic and regulatory subunits of PKA. Dissociate and FRET signal lost when cAMP binds.Hypothesised that cAMP microdomains might occur in T tubules of rat cardiomyocytes (Gs, AKAP-anchored PKA, ACs found throughout tubules).

Upon stimulation of β-ARs, saw a compartmentalised rise in cAMP in T-tubules.
Fagan et al. 1996
Shown in transfected HeLa cells that only capacitative Ca2+ entry could stimulate AC VIII.

ACVIII appears to be compartmentalised with CRAC channels.

Ca2+ released from stores does not access this AC isoform.
Masada et al. 2009
Studied different regulatory properties of AC1 and AC8.

Found AC1 localised to lipid rafts.

AC1 has slower regulation kinetics, possibly since NTD does not bind CaM.

AC1 gives steady increases in cAMP, AC* produces oscillatory rises - seen with FRET based sensor.

So equivalent Ca2+ signals can give rise to transient or steady cAMP rises depending on AC isoform.