cAMP signalling Flashcards
How cAMP signaling activated, what is cAMP, effector proteins, desensitisation
Cyclic AMP is a small molecule that serves as an intracellular second messenger of many hormones & neurotransmitters
Generate inside cells by the action of plasma membrane-adenylyl cyclase and quickly diffuses throughout cell (even through nucleus)
cAMP is detected by PKA effectors which phosphorylates target proteins EPAC, CNGCs, POPEYE and cAMP GEF
PDE is only family that degrades cAMP into AMP. Different localised degradation methods depending on type
cAMP production and degradation
Universal and ubiquitous signalling mechanism. 60 different Gs receptors expressed in different cell types with different physiological outcomes all produces cAMP
Gs coupled ligand bound receptor is activated so G alpha s is stimulated to bind and activate adenylyl cyclase to produces cAMP which binds to PKA and EPAC in cytoplasm.
PDE (‘sinks’) are highly specific and degrades cAMP in localised areas. If a receptor mediated event produces so much cAMP that PDE can’t cope, cAMP will increase in that area past the receptor threshold for activation
How is cAMP mediated signalling compartmentalised and examples
cAMP can have different physiological effects due to relationship between localisation of PDE, adenylyl cyclase and cAMP govern signalling.
Adenylyl cyclases (ACs) are localised to specific parts of the membrane (ex. lipid rafts) to produce cAMP locally.
Differential expression of PDEs for compartmentalisation. Ex. In nasal cavity of dogs, through staining specific proteins, saw AC3 (in membrane as expected), PDE4A in bottom of neurons so cAMP only affects protein that is likely near the top. PDE2 is not in nasal olfactory neurons (targeted to a different set of neurons)
AKAPs (A-kinase anchoring proteins) physically anchor PKA and other cAMP effectors to specific sites.
Selective expression of receptors (e.g., β1-adrenergic at the plasma membrane vs β2-adrenergic in T-tubules in heart cells) shapes where cAMP is made.
