Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Cell Biology > Intracellular Signalling > Flashcards

Intracellular Signalling Flashcards

You may prefer our related Brainscape-certified flashcards:
AP® Biology flashcards Biology 101 flashcards
1
Q

give a simplified overview of signalling?

A

a signal molecule will bind to a receptor and this will modulate a target protein

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

what is involved in intracellular signalling cascades?

A
  • use proteins interaction motives, kinases, phosphatases, GTPases
  • some can act in several different cascades
  • network rather than linear
  • allows control, diversification and cross talk
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

why are cell surface receptors important?

A

they initiate signalling cascades

- they receive and transfuse signals across the membrane

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

what are some examples of cell surface receptors?

A

G protein linked receptors

enzyme linked receptors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

what do cell surface receptors do?

A
  • cause a kinase cascade for example (from a G protein)

- signal onto second messengers (from enzyme)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

what is a GPCR?

A
  • around 500 in humans
  • have very diverse types of ligands
  • 50% of all drugs acto on GPCRs
  • affect every level of human physiology
  • receive a large range of signals
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

what ligands bind GPCRs?

A

amine hormones, peptides, small proteins, light, sugars and their derivatives

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

what is the structure of a GPCR?

A
  • conformational flexibility of beta adreneric receptor changes upon ligand binding
  • ligand binding, closes space at the extracellular side between TMs 3, 5 and 6
  • they are forced apart at the cytosolic side
  • induces a confomational change in the 5/6 loop coupling signal transduction
  • increased probability of something
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

how many families of trimeric G proteins are there?

A

3: I, II and III
- families are determined by amino acid sequences relatedness of the alpha subunits
- grouped due to their downstream targets or a specific GPCR type they are activated by

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

what are the functions of G proteins?

A
  • trimer G proteins bind GTP (hydrolyse) and then become activated
  • they have 3 subunits (alpha, beta and gamma)
  • the main one is the alpha subunit it binds GTP and is involved in signalling
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

what does the GPCR do?

A
  • receptor determines how a signal is interpreted
  • GPCR activates a G alpha protein
  • discovered using a chimeric GPCR
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

describe the experiment involving GPCR

A
  • adrenaline activates the alpa2 and beta2 adrenergic receptor
  • these actiavtes differe Galpha subunits
  • alpha2 activates G alpha i
  • beta2 activates a G alpha s
  • one inhibits a second messenger
  • other stimulates the same second messenger
  • same signal can exert different effects in specific cells by signalling through a different GPCR
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

how can you see these effects in GPCR in an experiment?

A

cut and past different parts of the receptors to see the effects

  • find its transmembrane helix 5,6
  • a loop between the two and a C terminus which are important
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

what happens once a Galpha protein is targeted?

A
  • can be stimulatory or inhibitory
  • both can couple to the downstream molecule adenylyl cyclase (a transmembrane protein)
  • enzymes which generate cAMP
  • when it couples GTP is hydrolysed and turn to GDP
  • some GPCRs activate adneylyl cyclase in adipose tissue whereas others inhibit it
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

can G proteins hydrolyse GTP?

A

they cant on their own they need other proteins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

describe what happens when a G protein binds to GPCR

A
  • activates and binds GTP
  • GPCR is GEF (guanine nucleotide exchange factor)
  • adenylyl cyclase: GTP activating proteins it activates
  • AC = GAP
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

what is the G protein cycle?

A
  • G proteins bind tightly to nucleotide co-factor
  • need GEF to release the GDP
  • GTP spontaneuosly binds, due to higher concentration in the cell
  • G proteins are GTPases - GTP hydrolysing enzymes - with extremely low activity so they need help from a GTPase activating protein (GAP)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

what can ADP ribosyltion occur?

A

it can permanently activate signalling

- permenently activated signalling has serious pathological conequences

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

how does the cholera toxin affect GPCR signalling?

A
  • colonises intestine
  • changes G alpha unit
  • catalyses covalent modification
  • adds ADP ribose from NAD+ to an arginine residue at the GTPase active site
  • prevents GTP hydrolysis by G alpha s and stimulatory G protein is permenantly activated
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

how does the Pertussis toxin affect GPCR signalling?

A
  • catalyses ADP ribosyltion at cystein residue of the inhibitory G alpha i
  • incapable of exchanging GDP for GTP
  • blocks inhibitory pathway
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

how are secondary messengers involved in signalling?

A
  • cAMP activates protein kinase
  • small molecules are produce or released upon activation
  • can activate downstream targets
  • amplify a signalling cascade
  • localized and constant destruction ensures a localized target response
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

what are the targets of cAMP?

A

pKA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

how does cAMP interact with pKA?

A
  • cAMP binding releases pKAs catalytic subunit and allows it to phosphorylate targets
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

describe pKA

A

3 isoforms of the catalytic subunit

4 isoforms of the regulatory subunit

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

how is glycogen metabolism controlled by enzymes?

A
  • glycogen phosphorylase, cleaves off glucose units - glycogen breakdown
  • glycogen synthase adds glucose units, glycogen synthesis (uses UDP glucosen lose energy)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

what are the effects of cAMP on glycogen dehydration?

A
  • activate GPCR with adrenaline
  • cascade to activate kinase A protein through cAMP
  • phosphorylates GPK which phosphorylates GP and breaks down glycogen
  • at the same time pKA inhibits glycogen synthesis
  • simultaneous activation of synthesis and inhibition of degradation
  • tightened control
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

what is an enzyme linked receptor?

A

on the binding of a ligand they activate some enzymatic activity on the cytosolic side

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

how do enzyme linked receptors work?

A
  • induce receptor dimerization
  • activates enzymatic activity
  • on cystolic side
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

how can receptor dimerization be induced?

A
  • mutual trans-phosphorylation of the two subunits

- recruitment of a catalytic subunit from the cytosol (becomes activated)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

what happens as a result of enzyme linked receptor becoming activated?

A

active enzyme may phosphorylate and activate targets - initiates a signalling cascade

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

what is RTK signalling?

A

receptor tyrosine kinase signalling - involves lots of domains
- it is a dimer needs dimerization

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

how does RTK signalling work?

A
  • it phosphorylates itself (2 halves trans phosphorylates)
  • fully activates receptor
  • recruits and activates proteins
  • activated receptor binds a multidocking proteins (IRS-1) and phosphorylates it
  • proteins recruited by their ability to bind phosphorylated tyrosine
  • their own tyrosines get phosphorylated as well
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

what roles does IRS-1 play in RTK signalling?

A
  • gets phosphorylated by RTK
  • provides further docking sites
  • recruits multiple factors would individually be inactiv
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

what are the 2 types of modules capably of binding phosphorylate tyrosine?

A

PTB (phosphotyrosine binding domain)

SH2 domain

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

what is PTB?

A
  • only has the property to bind the phosotyrosine
  • PTB domains are similar to each other
  • there are many
  • evolved from a common ancestor that was able to bind phosotyrosine
  • good feature
  • needs specificity
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

how does specificity work in PTB?

A

domains are specific to one phosphotyrosine

  • have amino acid residues in the vicinity
  • important for binding
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

how can phosphotyrosine binding switch signalling on or off?

A

it phosphorylates or dephosphorylates

38
Q

how does the insulin receptor work?

A
  • PTB of IRS1 binds specifically to Tyrp of the insulin receptor and IL4R
  • binding specificity - amino acid before the Tyr
  • Alanine (in IL4R) is best
39
Q

what are SH2 domains?

A
  • amino acids around pTyr provide a specificty signature
  • SHC needs a Leu or a Val at the third position of pTyr
  • amino acids after the pTyr at a specific distance
40
Q

what is phosphoinositide kinase mediated signalling?

A
  • one signalling molecule recruited by IRS1 is phosphoinositol 3 kinase (PI3K)
  • p85 subunit of PI3K contains an SH2 domain that binds phosphorylated IRS1
41
Q

what is the function of phospholipases?

A

PLC can transduce both GPCR and RTK initiated signal

42
Q

what is PLC activated by?

A

a G alpha protein or an activated RTK

43
Q

how does an activated RTK activated a PLC?

A
  • the RTK will dimerize
  • activated kinase domain
  • recruited PLC or γ(SHC 2 domain
  • promotes enzymatic activity of PLC gamma
  • its an enzyme that amplifies the signals
  • generates second messengers from an important signalling lipid
  • cross talks between GPCRs and RTKs
44
Q

what is the activity of PLC?

A
  • activated by GPCR or RTK
  • cleave a specific [PI(4,5)P2]
  • PLC doesnt have direct access to the [PI(4,5)P2]
  • when recruiteded in the same vicinty PLC can more easily find its target
45
Q

what is - [PI(4,5)P2]?

A
  • head groups is a sugar like molecule
  • many hydroxyls
  • one hydroxyl used to bind to the phosphate
  • other hydroxyls used as signalling platforms (depending on which is phosphorylated you get different signalling outcomes)
46
Q

what is the structure of - [PI(4,5)P2]?

A

contains a phosphate in the 4th and 5th position

47
Q

what happens when - [PI(4,5)P2] is PLC activated?

A
  • hydrolyses and cleaves between the glycerol and phosphate group that links the ring to the phospholipid backbone into DAG and IP3
48
Q

what is inositol 1,4,5 trisphosphate?

A

releases Ca2+ form the endoplasmic reitculum (ER)

49
Q

what is DAG?

A

activates protein kinase C remains membrane bound

50
Q

what is IP3?

A
  • diffuses to the ER
  • activates a channel to release Ca2+ ions
  • Ca2+ release is transient
  • increase Ca2+ concentration locally around the channel
  • released from the ER into the cytosol
  • IP3 degradation is by phosphates removing 4’ or 5’ or a kinase adding 3’
51
Q

can Ca2+ levels in the cytosol be generated chemically?

A

no

52
Q

why is Ca2+ important?

A

they are important second messengers

53
Q

describe Ca2+ in the cytosol?

A
  • low concentration in the cytosol
  • Ca2+ pumps it out of the cytosol to organelles or to the outside
  • Ca2+ channels in the plasma membrane and the ER when activated provide a local increase in cytosolic Ca2+ through IP3 gated channels from the ER
  • ER Ca2+ pumps constantly removes excess cytosolic Ca2+ into the ER
  • doesnt take long to get a large increase in calcium concentration
54
Q

where is Ca2+ signalling found?

A

Muscle contraction
neurotransmitter release
activation of calmodulin

55
Q

what is the activation of calmodulin?

A
  • important calcium binding protein
  • 2 different structures: one calcium free and one calcium bound
  • conformational cahnge
  • when it changes calcium binds to a kinase helix
  • activates the kinase and goes on to phosphorylate its targets
56
Q

what is the target of calcium?

A

protein kinase C (PKC)

57
Q

what is the conventional isoform of PKC?

A
  • alpha, beta, gamma
  • has a calcium binding domain
  • needs a second messenger to be activated and has a DAG binding domain
58
Q

what is the novel isoform of PKC?

A
  • need DAG only (activated)
59
Q

what is the atypical isoform of PKC?

A
  • activated by ceramide
60
Q

what can PKC affect?

A

adhesion, proliferation, differentiation, migration, apoptosis, autoimmunity, IgG switch

61
Q

give an overview of SH2

A
  • binds pTyr generated by receptor tyrosine kinase
  • once phosphorylated SH2 can bind
  • binding/not binding determine by phosphorylation state
  • specificity is determined by amino acids nearby
62
Q

what does insulin isgnalling do?

A

regulates metabolism

63
Q

what kind of receptor is the insulin receptor?

A

An RTK

64
Q

how does the insulin receptor function?

A
  • insulin (the ligand) binds and there is dimerization
  • activation of tyrosine kinase activity
  • phosphorylates the receptor
  • phosphorylates molecules that bind to the receptor via phosotyrosine binding
  • recruits proteins (IRS-1 which is a scaffolding protein)
  • recruits several different signalling proteins (makes sure they are next to each other)
65
Q

what does IRS-1 do?

A

provides docking sites for further signalling proteins and provides a further site for regulation

66
Q

how does phosphoinositide 3 kinase transmits insulin signalling?

A
  • recruited by IRS-1
  • the p85 subunit of PI3K contains and SH2 domain that binds phosphorylated IRS-1
  • important component of membranes
  • PI45 is a substrate for the kinase
  • creates binding sites for yet other domains
  • needs to recruit PI3 kinase to the membrane
67
Q

how does the local genertion of PI(3,4)p2 activates protein kinase B(PKB)?

A
  • recruits 2 proteins: PKB and PDK1
  • PDK1 phosphorylates PKB
  • PKB needs to be recruited and the phosphorylated
68
Q

what is PDK1?

A

phosphorylates PKB and contains a PH domain

69
Q

what is PKB?

A
  • needs to be recruited and then phosphorylated
  • in the cytosol (folded in on itself)
  • has a PH domain
  • binds and unfolds
  • PKB will be next to the PDK1
  • full activation of PKB
70
Q

what are some examples of PKB targets?

A
  • e.g. IRS-1, GSK3, GS, PDE3B, mTOR

- effects glycogen synthesis, protein synthesis, cAMP

71
Q

what is insulin?

A

reduces blood glucose levels so therefore the body wants to store glucose as glycogen
- mostly opposes adrenaline

72
Q

what is PD£?

A
  • inactivates PKA signalling
  • inactivates cAMP
  • degraded by phosphodiesterase (PDE)
  • signalling through adenylyl cyclase is antagonised by the continuous breakdown of cAMP through PDEs
  • ensures cAMP only acts when the cell is stimulated
73
Q

how are PDE’s regulated?

A

by themselves, PKA, PKB, calmodulin

- allows a further layer of regulation

74
Q

what is mTOR?

A
  • a kinase
  • central regulator of cell growth
  • TOR: target of rapamycin
75
Q

what is mTOR influenced by?

A
  • nutrients, insulin signalling

- protein synthesis, self-eating, respiration

76
Q

what does mTOR do?

A
  • regulates cellular metabolism
  • modulates how energy is used
  • physiologically (influences how we age)
  • oxidative stress if we take in too much
  • pathological = cancer
77
Q

what is rapamycin?

A
  • inhibiting TOR, strong influence on growth

- used as a drug for: immunosuppression, cancer, longetivity, psychiatric conditions

78
Q

what can be the negatives of mTOR?

A
  • overworking mitochondria produces reactive oxygen this can damage cells
  • mTOR activity has an effect on how quickly our cells age due to damage
  • highlevels = obesity
  • restrict calroic intake, to a degree, live longer
  • medication that does the same thing as limiting calorie intake that inhibits mTOR
79
Q

how does insulin affect glycogen synthesis?

A
  • insulin and adrenaline come together at the same target, insulin receptors take charge
  • IRS-1
  • p85 and p110 (PI3 kinase)
  • activates PDK1
  • inhibits PGSK3 (activates glycogen synthase)
80
Q

how does adrenaline affect glycogen synthesis?

A
  • switches off insulin signalling

- short term signalling effects

81
Q

how do the intracellular signals cross talk?

A
  • PKA, PKC, CAM kinase etc all have common targets
  • can be phosphorylated by more than one of these kinase
  • can phosphorylate and regulate members of other pathways
  • PLC is a common component of GPCR and RTK signalling
82
Q

how does PKB inactivate IRS-1?

A
  • negative feedback

- inhibits cAMP and affects glycogen synthase

83
Q

why is compartmentalisation important?

A
  • allows streamlining of cross talk

- recruiting activated signal transducers and targets to the same place (endosomes) where signalling can be channelled

84
Q

what do EEA1 and APPL do?

A

they are scaffolds that bind to endosomal PIPs

85
Q

what is endosomal recruitment?

A

endosomal recruitment of activated Akt promotes cell survival rather than growth by presenting Akt with a different substrate

86
Q

what is endosomal activation?

A

Akt by the MAPK pathway leads to overgrowth (hypertrophy)

87
Q

describe receptor down regulation by sequestration

A
  • release of the ligand is not promoted in the endosome
  • receptors are delivered to the multivescular body (MVB)
  • MVBs have internal vesicles (formed from invaginations of their own limiting membrane)
  • once in the internal vesicle of MVB the receptors active cytosolic portion is sequestered from the cytosol portion is sequestered from the cytosol
  • the physical separation stops signalling
  • receptors in MVBs can be degraded or recycled
88
Q

what is ubiquitin?

A
  • surface receptors are often ubiquintinylated following prolonged stimulation
  • monoubiquitinylation of receptors induces their endocytosis
  • endosome often provides a second signalling patteren
  • sequestered into internal vesicle of a compartment called the MVB
89
Q

Name a key signalling protein that ensures efficient cross talk between the insulin and adrenaline signalling pathways

A

PDE

90
Q

list four ways in which a cell surface receptors downstream signalling can be modulated

A
  • Extracellular ligand binding (followed by dimerization and/or conformational change in the TM region)
  • Internalization (following ubiquitinylation)
  • Phosphorylation
  • Binding of an intracellular accessory protein (e.g. arrestin, scaffolding protein)
91
Q

What is the role of the phosphotyrosine residue for signal transduction via the PTB and SH2 domains?

A

It is an on/off switch for signalling

92
Q

What are the three key features that allow Ca2+ to be used as a second messenger?

A
  • Cytosolic concentration of Ca2+ is 1000-fold lower than in organelles or outside of the cell
  • Ca2+ specific channels respond to signalling molecules (e.g. IP3)
  • Ca2+ binding can cause large conformational changes in the targets of Ca2+ signalling

Cell Biology (10 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions