G-Protein-coupled Receptors

- receptor kinase phosphorylates at the cytosolic site of the receptor - arrestin binds to pi sites to inactivate the receptor - arrestin as adaptor for clathrin-mediated endcytosis

- alpha subunit has GTPase activity and hydrolyzes bound GDP to GTP (reassociates w/ beta-gamma-complex) which returns everything to inactive conformation - regulator of G-protein signaling (RGS) accelerates GTP hydrolysis

- bacteria in gut modify alpha unit so it can't hydrolyze GTP and is on indefinitely - prolongs the signal so adenylyl cyclase makes cAMP and continue of things into the gut= diarrhea - bacteria in lung alter the alpha unit so it remains in GDP-bound state to inhibit adenylyl cyclase -coninously inactive= prolonged signal

- adenylyl cyclase= cAMP - phospholipase C= inositol triphosphate and diacylglycerol

- enzyme activated by cAMP (conformational change) - then when activated, catalyzes the phosphorylation of particular serines or threonines

- binds and opens ER Ca2+ channels - increases the concentration of Ca2+ in the cytosol - mimicked by Ca2+ ionophores

- combining with Ca2+ it activates protein kinase C - C-kinase Pi intracellular proteins - mimicked by phorbol esters

- most widespread Ca2+-responsive protein - binds to Ca 2+ which causes a conformation change that allows it to bind to target proteins and change their activity

- activated by calmodulin and then phosphorylate select proteins ex. in mice, neuron specifc - abundant in synapses, w/o it can't remember

- allow cells to be sensitive to signal intensity change in signaling pathways 1. alteration of receptor number and activity 2. changes in downstream events

1. receptor down-reguation (destroy in lysosome after internalization) 2. receptor inactivation (arrestin) 3. receptor sequestration (receptor is internalized so it has no access to ligand)