signaling through G protein coupled receptros Flashcards
what are second messenger molecules and examples?
heterotrimeric G proteins stimulate/inhibit downstream effectors through second messenger molecules.
cAMP, cGMP, IP3, DAG, Ca2+
what stimulates/inhibits adenylyl cyclase? what does adenylyl cyclase do?
there are 9 forms of adenylyl cyclase. GalphaS stimulates all 9 and Galphai inhibits some. adenylyl cyclase synthesizes cAMP from ATP via its intracellular catalytic domain.
two types of Guanylyl cyclase enzymes. what does Guanylyl cyclase do?
type 1: membrane bound. include external binding domain, transmembrane domain, and intracellular domain
type 2: soluble. fully intracellular, activated by NO gas
both types synthesize cGMP from GTP.
what are phophodiesterases (PDEs)?
PDEs are enzymes that degrade either cAMP and/or cGMP. They counterbalance production of cAMP and cGMP. cAMP is degraded to 5’-AMP (inactive)
how is protein kinase A activated?
cAMP bind to regulatory subunits and allow them to dissociate from the catalytic subunits. The catalytic subunits are active only after dissociation.
what are the long term effects of cAMP? (protein kinase A)
cAMP activates protein kinase A (PKA) which then enters the nucleus and phosphorylates CREB. CREB binds CBP and act as transcription factors, binding a CRE located in a promotor region of a gene.
Basically activated PKA causes more gene transcription and this leads to long term effects.
how are IP3 and DAG produced?
PI(4,5)P2 is cleaved by phospholipase C-beta 1 (PLCB1) to form IP3 and DAG
what do IP3 and DAG do?
IP3 binds to receptors on the ER and allow Ca2+ to exit. DAG and Ca2+ activate Protein kinase C, which plays a role in signal transduction cascades
How is Ca2+ propagated through a cell?
as a wave created by a regenerative Ca2+ induced Ca2+ release mechanism. Calcium does not stay released for long and will be released from the cell or stored. cytosolic calcium is low
What are a couple of mechanisms that keep cytosolic calcium low?
calcium can be actively removed by pumps or taken back into ER by pumps (Ca2+-ATPases), moved against electrochemical gradient outside the cell or into mitochondria by exchangers (Na+/Ca2+ exchangers), and through binding molecules in cytoplasm
what is calmodulin?
Calmodulin (CaM) exists in the cytosol and may activate/inactivate its downstream effector proteins after Ca2+ activates. CaM modulates many Ca2+ pathways
describe the CaMK example of calmodulin effects
Calmodulin kinase (CaMK) is a serine/threonine protein kinase activated by CaM binding. Once activated CaMK can phosphorylate other proteins at serine/threonine residues. CaMK becomes independent of Ca2+ eventually as its subunits activate.
