foundation I Flashcards
(10 cards)
implication of 2nd law of thermodynamics for cells
- 2nd law states that total entropy of a system increases over time
(i.e. tends towards DISORDER) -
INPUT of energy is required to counteract entropy
and maintain the highly organised stuctures found in cells
which of the following ligands bind to intracellular receptors?
A) water-soluble hormones (e.g. insulin, epinephrine)
B) cytokines (e.g. JAK-STAT)
C) lipophilic hormones
D) growth factors (e.g. TGF)
ligands must diffuse across the lipid bilayer to do so
C) lipophilic hormones
examples include
* steroid hormones (e.g. estrogen)
* thyroid hormone
* vitamins (e.g. vit D, retinoic acid — active form of vit A)
describe Ras-MAPK signaling pathway:
1. binding of (…) to Receptor Tyrosine Kinase (RTK) on cell surface
2. inducing (…) and thus activation of RTK
3. intracellular (…) domains of RTKs then undergo (…)
4. which allows it to bind (…)
5. and subsequently activate (…) by binding to it and promoting the exchange of (…)
6. ending in the MAPK cascade ((…) -> (…) -> (…) -> (…))
7. (…) then translocates to nucleus and activates transcription factors
- binding of growth factor to Receptor Tyrosine Kinase (RTK) on cell surface
- inducing dimerization and thus activation of RTK
- intracellular tyrosine kinase domains of RTKs then undergo auto or cross-phosphorylation
- which allows it to bind adaptor proteins
- and subsequently activate Ras by binding to it and promoting the exchange of GDP for GTP
- ending in the MAPK cascade (Ras -> Raf -> MEK -> ERK)
- ERK then translocates to nucleus and activates transcription factors
describe PI3K-Akt signaling pathway:
1. binding of (…) to Receptor Tyrosine Kinase (RTK) on cell surface
2. inducing (…) and thus activation of RTK
3. intracellular (…) domains of RTKs then undergo (…)
4. which creates docking sites for (…)
5. which is thus activated,
and subsequently phosphorylates (…)
6. (…) acts as a docking site to recruit (…) and (…)
7.(…), along with another enzyme, then phosphorylates and fully activates (…)
8. (…) then phosphorylates various downstream targets involved in cell survival, cell growth, metabolism, etc
- binding of growth factor to Receptor Tyrosine Kinase (RTK) on cell surface
- inducing dimerization and thus activation of RTK
- intracellular tyrosine kinase domains of RTKs then undergo auto or cross-phosphorylation
- which creates docking sites for phosphoinositide-3-kinase (PI3K)
- which is thus activated,
and subsequently phosphorylates PIP2 -> PIP3 - PIP3 acts as a docking site to recruit Akt and PDK1
7.PDK1, along mTOR, then phosphorylates and fully activates Akt - Akt then phosphorylates various downstream targets involved in cell survival, cell growth, metabolism, etc
link!
metabolism: insulin acts via PI3K pathway to
* ↑GLUT4 transporters and ↑K+ uptake
* ↑ protein synthesis
* ↑ glycogen synthesis
which pathway does mutation in PTEN affect
and how
LOF in PTEN
→ reduced dephosphorylation of PIP3 -> PIP2
→ accumulation of PIP3
→ hyperactivation of Akt and mTOR
⇒ uncontrolled cell growth and proliferation
Which one of the following activating variations will MOST LIKELY be observed in cancer cells?
A) Increased Ras exchange of GTP for GDP
B) Increased phosphorylation of Raf kinase
C) Increased nuclear translocation of Ras
D) Decreased dimerization of the Ras
E) Decreased binding of Ras to Erk
B) Increased phosphorylation of Raf kinase
the change will always be Ras remaining in active GTP-bound state
→ constant activation of Raf, then MEK and finally ERK
→ ERK translocates to nucleus and promotes gene transcription for uncontrolled cell division
describe GPCR signaling pathway:
1. ligand binds to extracellular domain of GPCR
2. inducing a (…) and thus activation of the (…) bound to GPCR,
and thus resulting in exchange of (…)
and the dissociation of the (…) subunit from the (…) subunit
3. the (…) subunit then activates (…),
which converts (…)
4. (…) then activates (…),
which goes on to phosphorylate target proteins
- ligand binds to extracellular domain of GPCR
- inducing a conformational change and thus activation of the G-protein bound to GPCR,
and thus resulting in exchange of GDP for GTP
and the dissociation of the α subunit from the βγ subunit - the α subunit then activates adenylyl cyclase,
which converts ATP to cAMP - cAMP then activates protein kinase A (PKA),
which goes on to phosphorylate target proteins
notice that I didn’t say GPCR signaling pathway
apply G protein signaling pathway to toxic effects of vibrio cholerae
bacterium found in contaminated food
produces cholera toxin
→ activates α subunit of G protein
(NOT via binding to GPCR)
→ which then activates adenylyl cyclase
→ which converts ATP -> cAMP
→ which goes on to activate PKA
→ which phosphorylates CFTR chloride channel
→ efflux of Cl- and water from intestinal CELLS to intestinal LUMEN
⇒ diarrhoea
describe GPCR signaling pathway:
1. ligand binds to the extracellular domain of (…)
2. inducing a (…) and thus activation of the (…) ((…) subtype) bound to GPCR,
and thus resulting in exchange of (…)
and the dissociation of the (…) subunit from the (…) subunit
3. the (…) subunit then activates (…),
which converts (…) into (…) and (…)
4. (…) then activates receptors on the (…),
which releases (…) into the cytosol,
while (…) activates (…),
which goes on to phosphorylate target proteins
- ligand binds to the extracellular domain of GPCR
- inducing a conformational change and thus activation of the G protein (Gq subtype) bound to GPCR,
and thus resulting in exchange of GDP for GTP
and the dissociation of the α subunit from the βγ subunit - the α subunit then activates PLC,
which converts PIP2 into IP3 and DAG -
IP3 then activates IP3 receptors on the ER,
which releases Ca²⁺ into the cytosol,
while DAG, along with Ca²⁺, activates protein kinase C (PKC),
which goes on to phosphorylate target proteins
how is GPCR signaling terminated
α subunit hydrolyses GTP to GDP
→ return of G-protein to inactive state
→ also reassociation of α and βγ subunits
