Signal transduction Flashcards
Describe G protein structure
trimeric
A, B, G subunits (beta and gamma stick together)
water soluble with FA attach to PM
GTP/GDP binding at alpha chain
structure of GPCR
(g coupled protein receptor)
7 TM domains, intracellular look that associates w G prot
What are the different types of cell surface receptors? (3)
GPCR
Enzyme linked receptors (tyrosine kinases)
Ion channel coupled receptors
G(s)
- active subunit
- function
- alpha
- activate adenylyl cyclase
G(i)
- active subunit
- function
- alpha
- inhibits adenylyl cyclase
G(0)
- active subunit
- function
- beta gamma
- activates K+ channels, activates phospholipase C
What does adenylyl cyclase activation do?
Activates second messenger system
What does enzyme linked receptor binding usually do?
cell growth, proliferation, differentiation, survival
signal molecules are called “growth factors”
What types of molecules bind enzyme linked receptors?
growth factors
What is most common enzyme linked rececptor?
Receptor tyrosine kinase
What are intracellular receptors? what do they bind? where do they go? give examples (3)
small hydrophobic molecules diffuse across membrane
bind receptor
carried to nucleus
ex. steroid hormones, thyroid hormones, retinoids
Name the 3 ways to carry info from extracellular to intracellular?
Cell surface receptors
Intracellular receptors
Gases
How is NO generated?
arginine via NO synthase (NOS) in endoethelial cell
What are the effects of NO?
localized, paracrine effects; can diffuse across PM
bind guanylyl cyclase (GTP–> cGMP) –> vasodilation
also iimportant for vision
What do we use nitroglycerin to treat?
angina (not enough blood to heart)
What is signal transduction?
When extracellular signnal makes change inside cell
What does a second messenger allow a cell to do during signal transduction?
diffuse signal throughout cell
What does adenylyl cyclase do?
activate PKA pathway
ATP–> cAMP
cAMP activates PKA (hangs out in cytosol or goes to nucleus)
what does cAMP phosphodiesterase do?
cleaves cAMP–> AMP (constantly active)
How does cholera work?
cholera binds Gs protein in intestine –> GTP permanent binding –> tons of cAMP –> water flow to lumen –> diarrhea
How does fear increase heart rate?
epi/norepi binding at Gs type GPCR (beta adrenergic receptors)–> PKA pathway –> phosphyrlates heart cell regulators
Second messenger system involving PI?
- PI phosphorylated by PI kinase –> PIP2
- cleave part of PIP2 in cytosol –> diacylglycerol (DAG; still in PM) + inositol triphosphate (IP3)
- DAG can activate PKC; IP3 opens Ca2+ channels
RAS signaling cascade
- receptor tyrosine kinase –> phosphorylate adaptor protein
- adaptor protein is scaffold for RAS activation (GTP binding)
- RAS activates MAP kinnase cascade (3 kinases)
-RAS mutation is oncogene
PI3 kinase pathway
RAS actviate PI3 kinase –> cell growth and survival
PI3 kinase phosphorylates PI (PI–> PI3)
PI3 vs IP3
PI3 stays on membrane; part of RAS/PI3 kinase pathway
IP3 is part of PI that is cleaved from membrane; is a second messenger
JAK-STAT pathway
-JAK-STAT receptor crossphosphorylates; then phosphorylates itself
-recruits STAT proteins; activated and dimerize
-STAT goes to nuclues
(is a tyrosine kinase receptor)
What binds JAK-STAT?
Cytokines
- gamma interferon (macrophage activation)
- alpha interferon (viral infection immunity)
- erythropoietin
- growht hormone (stim growth)
TGF-beta pathway
development
- serine/threonine kinase
- dimerize and transphophorylation–> recruit/activate SMAD proteins –> couple and go to nucleus
Describe inactivation of GPCR in heart
- G protein couple receptor kinase (GRK) phosphorylates beta adrenergic receptor (only when receptor is ligand bound)
- causes arrestin to bind, blocking G protein
Heart damage messes with this –> weakened heart rate
Which signal receptor is normally a dimer?
Insulin receptor
Insulin receptor pathway
- Insulin binding -> cross phosphorylation (receptor tyrosine kinase) –> recruits and phosphoryyalte insulin receptor substrate (IRS)
- IRS binds PI3 kinase (activates); IRS activates PIP2 –> PIP3
- PIP3 activates AKT kinase –> –> GLUT 4 transport to PM and glycogen synthasee activation
