Signal transduction Flashcards

0
Q

Describe G protein structure

A

trimeric
A, B, G subunits (beta and gamma stick together)
water soluble with FA attach to PM
GTP/GDP binding at alpha chain

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1
Q

structure of GPCR

A

(g coupled protein receptor)

7 TM domains, intracellular look that associates w G prot

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2
Q

What are the different types of cell surface receptors? (3)

A

GPCR
Enzyme linked receptors (tyrosine kinases)
Ion channel coupled receptors

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3
Q

G(s)

  • active subunit
  • function
A
  • alpha

- activate adenylyl cyclase

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4
Q

G(i)

  • active subunit
  • function
A
  • alpha

- inhibits adenylyl cyclase

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5
Q

G(0)

  • active subunit
  • function
A
  • beta gamma

- activates K+ channels, activates phospholipase C

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6
Q

What does adenylyl cyclase activation do?

A

Activates second messenger system

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7
Q

What does enzyme linked receptor binding usually do?

A

cell growth, proliferation, differentiation, survival

signal molecules are called “growth factors”

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8
Q

What types of molecules bind enzyme linked receptors?

A

growth factors

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9
Q

What is most common enzyme linked rececptor?

A

Receptor tyrosine kinase

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10
Q

What are intracellular receptors? what do they bind? where do they go? give examples (3)

A

small hydrophobic molecules diffuse across membrane
bind receptor
carried to nucleus
ex. steroid hormones, thyroid hormones, retinoids

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11
Q

Name the 3 ways to carry info from extracellular to intracellular?

A

Cell surface receptors
Intracellular receptors
Gases

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12
Q

How is NO generated?

A

arginine via NO synthase (NOS) in endoethelial cell

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13
Q

What are the effects of NO?

A

localized, paracrine effects; can diffuse across PM
bind guanylyl cyclase (GTP–> cGMP) –> vasodilation
also iimportant for vision

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14
Q

What do we use nitroglycerin to treat?

A

angina (not enough blood to heart)

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15
Q

What is signal transduction?

A

When extracellular signnal makes change inside cell

16
Q

What does a second messenger allow a cell to do during signal transduction?

A

diffuse signal throughout cell

17
Q

What does adenylyl cyclase do?

A

activate PKA pathway
ATP–> cAMP
cAMP activates PKA (hangs out in cytosol or goes to nucleus)

18
Q

what does cAMP phosphodiesterase do?

A

cleaves cAMP–> AMP (constantly active)

19
Q

How does cholera work?

A

cholera binds Gs protein in intestine –> GTP permanent binding –> tons of cAMP –> water flow to lumen –> diarrhea

20
Q

How does fear increase heart rate?

A

epi/norepi binding at Gs type GPCR (beta adrenergic receptors)–> PKA pathway –> phosphyrlates heart cell regulators

21
Q

Second messenger system involving PI?

A
  • 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
22
Q

RAS signaling cascade

A
  • 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

23
Q

PI3 kinase pathway

A

RAS actviate PI3 kinase –> cell growth and survival

PI3 kinase phosphorylates PI (PI–> PI3)

24
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
25
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)
26
What binds JAK-STAT?
Cytokines - gamma interferon (macrophage activation) - alpha interferon (viral infection immunity) - erythropoietin - growht hormone (stim growth)
27
TGF-beta pathway
development - serine/threonine kinase - dimerize and transphophorylation--> recruit/activate SMAD proteins --> couple and go to nucleus
28
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
29
Which signal receptor is normally a dimer?
Insulin receptor
30
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