adenylyl cyclase cascade Flashcards
what role does adenylyl cyclase play in the activation pathway
effector protein
what is the cascade that leads to phosphorylation by PKA?
the ligand binds to the receptor, activating the trimeric g protein. this causes a change in adenylyl cyclase activity, triggering a change in cAMP second messenger which activates PKA which phosphorylates a target
what are the stimuli which can lead to glycogen breakdown through G protein activation
glucagon and adrenaline stimulation in the hepatocytes or muscle cells
how can adenylyl cyclase be inhibited
adenylyl cyclase can also be inhibited via g protein activation of an inhibitory g protein complex activated by hormones such as PGE1 and adenosine
describe the structure of PKA
integral membrane protein with 2 integral domains, 2 catalytic domains on the cytosolic face.
which domains of PKA are activated by the Ga subunit of the stimulatory pathway?
catalytic domains
how is cAMP generated and inactivated?
idk
which PKA subunit does cAMP bind to and how does it activate it?
4 cAMP molecules bind to the integral regulatory subunits (2 per subunit)
what state is PKA in at high cAMP levels?
activated
what state is PKA in at low cAMP levels and what happens instead?
inactive, PP is activated
what enzymes do activated PKA activate and inhibit?
activates key enzymes in glycogen breakdown and inhibits key enzymes in glycogen synthesis
what enzymes do activated PP activate and inhibit?
activates key enzymes in glycogen synthesis and inhibits key enzymes in glycogen breakdown
how can hormones be effective even at low concentrations or low receptors number
signal amplification
what molar concentration of adrenaline is required for glycogenolysis and glucose release?
10-10 M
what are the mechanisms behind GCPR down regulation?
increased intrinsic GTPase activity in the Ga subunit, increased GTPase activity when bound to adenylyl cyclase, increased PDE activity
what is homologous desensitisation?
desensitisation of a receptor due to over exposure to its own ligand
what is heterologous desensitisation?
desensitisation of a receptor due to overexposure of a different receptor that triggers the same physiological response
what can be the result of extensive receptor desensitisation?
when the receptor has been extensively phosphorylated this can allow binding of B-arrestin which inhibits further G protein activation and promotes endocytosis where the receptor can be recycled or degraded. B arrestin may also activate an alternate pathway
what is the function of an A-Kinase Anchoring Protein (AKAP)?
localisation of the effects of cAMP to specific cell regions
why is subcellular compartmentalisation necessary to cell function?
cAMP is able to trigger a number of responses in the cell which are only needed in certain areas. dynamic regulation requires the ability to terminate reactions quickly
what are the domains in AKAPs?
domain confering specific subcellular location, PKA regulatory subunit binding domain
