GPCR Signaling Flashcards
Example of paracrine signaling?
- growth factors from prostate stromal cells
- elicit growth of neighboring prostate epithelial cells
What second messengers does PLC generate?
- Diacylglycerol (DAG)
2. Inositol 1,4,5-triphosophate (IP3)
What does DAG activate?
PKC
What does IP3 activate?
- release of Ca2+ from ER
Receptors assoc w/ G(as) and G(ai)?
- stimulatory = beta adrenergic
- inhibitory = alpha adrenergic
Briefly describe steps in PKA pathway after PKA activated (4)
- active PKA catalytic subunits enter nucleus and phosphorylate transc factor cAMP Response Element Binding (CREB) protein
- phosph-CREB binds to cAMP response element (CRE) DNA consensus seq’s
- CREB binding protein (CBP)/p300 transc factors bind CREB and assoc w/ basal transc machinery
- mediates transc of CRE-containing genes
What other kinase does PKA activate? What are its functions? (2)
- Mitogen-Activated Protein Kinase (MAPK)
- phosphorylates transc factors to change gene expression
- phosphorylates target proteins to change enzyme activities
In what 3 tissue types is Epi/glucagon the stimulatory GPCR hormone?
- adipose
- liver
- skeletal mm
In what tissue types does GPCR signaling –> release of other hormones? (3)
- ovary
- adrenal
- thyroid
Mechanism of cholera toxin? (5)
- mod’s G(as) subunit –> constant activity of AC, cAMP, and PKA
- activation of CFTR channel in intestinal epithelial cells
- Cl- ions flow into intestinal lumen
- followed by H2O
- chronic H2O loss – watery diarrhea
Mechanism of Bordatella pertussis (Whooping cough)?
- Purtussis toxin mod’s a G(ai) subunit (inhibitory)
- prevents GDP release from inhibitory G protein
- cont inactivation of inhibitory signal
- cont increase in AC, cAMP, and PKA activity
- activates CFTR channel in lungs –> fluid lost in mucous secretion
Mechanism of Propranolol beta blocker? (4)
- inhibits beta-adrenergic signaling
- re-establishes proper cytosolic:SR rations of Ca2+ stores
- improves cardiac contractile function
- tx for heart issues
What chain of events are DAG and IP3 derived from? (2)
- PI on C-leaflet of PM phos’d into PIP2
- PIP2 is substrate for PLC –> DAG (membrane) and IP3 (cytosol)
How does Ca2+ facilitate PKC activation? (2)
- helps bring PKC to PM surface
- activated by DAG
Sequence of smooth mm relaxation? (8)
- ACh binds GPCR
- PLC activated –> IP3 and DAG
- IP3 –> release of Ca2+
- Ca2+ complexes w/ Calmodulin
- complex activates NO synthase –> NO
- NO diffuses to neighboring cells and binds NO receptr
- activates GC, cGMP, and PKG
- PKG relaxes smooth mm cells and dilates blood vessels
