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Advanced Cells > lec 10-11 signalling pathways > Flashcards

lec 10-11 signalling pathways Flashcards

1
Q

GPCR

A
  • 7 transmembrane domains
  • recognise external signals
  • more than 700 in the genome
  • important for sight, smell, taste
  • target for over half of medical drugs
  • change in 3D structure when binding
  • act as an exchange factor (GEF) to induce exchange of GDP for GTP on a series of specific trimeric G proteins
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2
Q

heterotrimeric G proteins

A

3 subunits - alpha, beta, gamma

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3
Q

alpha subunit

A

activated when GTP bound
dissociates from beta-gamma complex
interacts with and activates target enzyme in membrane

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4
Q

when alpha subunit hydrolyses GTP over time

A

becomes inactivated
cleaves target protein
re-joins beta-gamma complex
target enzyme remains active and continues to signal in cell

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5
Q

many GPCRs are coupled to stimulatory trimeric G proteins - Gs

A

activate membrane bound adenyl cyclase
produce 2nd messenger cAMP from ATP
cAMP conc. rapidly increases

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6
Q

phosphodiesterase

A

converts cAMP to ATP

switches off signal

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7
Q

PKA

A

protein kinase A

inactive tetramer of 2 catalytic subunits and 2 inhibitory subunits

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8
Q

when cAMP binds to PKA

A

inhibitory subunits released
kinase subunits activated
signal transmitted from outside to inside cell

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9
Q

adaptor proteins and PKA

A

localised PKA to specific places in the cell

allowing rapid response

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10
Q

activated kinase subunits phosphorylate target proteins - fast acting

A

activate phosphodiesterase

cAMP acts as a switch

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11
Q

activated kinase subunits phosphorylate target proteins - slow ones

A

binds and phosphorylates CREB

targets transcription in nucleus

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12
Q

phospholipase C

A

membrane bound protein
activates by trimeric Gq proteins
acts on phospholipids

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13
Q

PLC cleaves leaving diaglycerol in the membrane …

A

IP3 interacts with Ca channels in the ER
Ca released and activates protein kinase C

increased Ca in cytoplasm

protein kinase C continues cascade with phosphorylation

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14
Q

3 mechanisms that keep Ca conc low in cytosol

A

ATP dependent Ca pump in ER membrane

Ca binding molecules in cytoplasm

active Ca import in matrix of mitochondria

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15
Q

high Ca2+ conc

A

calcium release inhibited

cA stored again

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16
Q

calmodulin

A

flexible protein structure
allows easy interaction with other proteins - activates them
binds calcium - causes conformational change
switch like activation
phosphorylates itself to become fully active

17
Q

Ca acts as 2nd messenger

A

activates specific calcium dependent kinase

18
Q

receptor tyrosine kinases

A

used to transmit signals from hormones/growth factors

19
Q

RTK targets

A

small GTPases

PI 3-kinase

20
Q

small GTPases

A

Ras and Rho

anchored to plasma membrane - cytoplasmic side
activated by pTyr binding to docking proteins
MAP kinase cascade pathway activated by Ras

21
Q

PI 3-kinase

A

PI

  • inositol head group
  • allows reversible phosphorylation

produces intermediates with carbon-3 phosphorylated

PIP2 cleaves from phospholipase 3 pathway - generates PIP3

22
Q

examples of 2nd messengers

A

cyclic nucleotides
lipids
cations

23
Q

PIP3

A

generated when PIP2 cleaves fro phospholipase 3 pathway

interacts with target proteins through ‘pleckstin homology’ domains

24
Q

MP kinase cascade pathway

A

activated by Ras

25
Q

mTOR protein

A

mammalian target of Rapamycin

mTORC1 and mTORC2

26
Q

Rapamycin

A

bacterial toxin
targets and inactivates mTOR kinase
inhibits cellular growth

27
Q

activation of mTOR

A

RHEB-GTP

RHEB is a small GTPase

28
Q

regulation of RHEB

A

TSC1/TSC2
inhibitors of mTOR

inactivates RHEB, stimulates GTP hydrolysis, acts as a GAP towards RHEB
mTOR not activated

29
Q

control of TSC

A

Akt phosphorylates or inhibits TSC when active
mTOR then signals downstream
activated via receptor TKs, PIP3 - PDK kinase activated - Akt kinase activated

30
Q

mTOR signalling pathway with growth factor

A

active PIP3 kinase
active Akt
inactive TSC2
activation of RHEB

active mTOR - cellular growth

31
Q

mTOR signalling pathway without growth factor

A

no activation of Akt by growth factors
active TSC
inactivation of RHEB

inhibition of mTOR - no cellular growth

32
Q

mechanism to avoid apoptosis in times of cell starvation

A

cell degrades itself

autophagy

33
Q

mTORC1

A

promotes protein synthesis - binds to mRNA and initiates translation

promotes ribosome production -

inhibits protein degradation

34
Q

mTORC2

A

acts on actin cytoskeleton and cell shape

35
Q

kinases that are downstream targets of mTOR

A

S6 kinase
- ribosomal protein/increases ribosomal assembly

elF4E - translation initiation factor
- elongation factor

36
Q

uncontrolled mTOR pathway leads to..

A

tuberous sclerosis

mutations in TSC1/2 complex - genetic disease
cellular growth uncontrolled
tumour formation in vital organs

37
Q

insulin signalling pathway

A

receptor tyr kinase found on insulin responsive cells

2 alpha and 2 beta subunits

Advanced Cells (10 decks)

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