Brainscape's Knowledge GenomeTM

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


See full index

Biomed 2 > Cell Bio - Intracellular signalling > Flashcards

Cell Bio - Intracellular signalling Flashcards

1
Q

what does FRET show

A

shows that proteins tethered to the lipid membrane interact more

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

what does FRET (fluorescent resonance energy transfer) dependant on

A

depends on the distance of the flurophores
must be within approx. 10 nm

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

what drives cell transformation

A

forced membrane localisation of PKB

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

concerning protein localisation at the membrane what are the phosphobinding motifs and what is the other type of binding motif

A

SH2
PTB
ubiquitin binding motif

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

what is AKAP interaction domain

A

interaction between a cytosolic and membrane bound protein

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

concerning lipid interaction motifs, what are the phosphoinositide interacting motifs

A

PH
FYVE
PX
PHD
lysine - arginine (K-R) rich patches

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

in terms of protein-membrane localisation, what are the mechanisms used to control lipid tether at the membrane

A

myristoylation
prenylation

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

single lipid tethers are often not stable enough, how is this problem rectified

A

lipid tether is compined with lipid interaction motifs to induce stable localisation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

what is fatty acylation

A

mainly consists of the addition of myristic or palmitic fatty acids to a protein

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

how is myristate bound to the protein

A

bound to the N-terminal glycine residue via an amide bond
irreversible

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

what is step 1 in myristoylation

A

removal of the N-terminal methionine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

step 2 of myristoylation

A

activation of myristic acid via CoA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

step 3 of myristoylation

A

coupling of myristic acid to glycine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

what is the role of myristoylation in apoptosis

A

1 - caspase mediated cleavage of Bid exposes a glycine
2 - Bid is myristoylated
3 - lipid tether induces insertion into mitochondrial membrane
4 - recruitment of BAK to the mitochondrial membrane
5 - cytochrome-C is released
6 - apoptosis downstream

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

to what does prenylation occur

A

to proteins containing a CAAX motif on their C-terminus

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

what is a CAAX motif and what does it generate

A

C - cystine residue, functions as isoprenoid attachment
A - signifies any aliphatic amino acid
X - any of several amino acids
generated a thioether linkage

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

how is prenylation initiated

A

by the attachment of farnesyl/geranylgeranyl to the cystine residue via farnesyltransferase or garenylgeranyltransferase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

how can a prenylated protein be further processed

A

RAS-converting CAAX endopeptidase 1 (RCE1) which removes the -AAX residues

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

what is the function of isoprenylcysteine carboxylmethyltransferase (ICMT)

A

caps the carboxy group on the now C-terminal isoprenoid-modified cystine residue
using a methyl group

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

what is Kras4B targeted to and how

A

targeted to PM
via interactions with its polybasic region with phosphoinositides

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

how often is Ras mutated in human tumours and where

A

16%
mutation in codon 12,13 and 61

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

why do H and N Ras undergo prenylation and palmitoylation

A

to target them stably to the membrane

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

how does Kras get targeted stably to the membrane

A

only undergoes prenylation
uses PRB for stable association to the membrane

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

what is progeria syndrome such as Hutchinson-Gilford (HGPS) caused by

A

abnormal processing of the CAAX protein
prelamin A

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

what can be used to treat HGPS

A

Ftase inhibitors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

effects of adrenergic activation

A

Increase strength and heart rate
Increased blood flow to muscle
Increased systemic and cellular energy supply
Increased skeletal muscle force
decreased gut motility
decreased peripheral blood flow

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

what releases norepinephrine

A

sympathetic nervous system post-ganglionic fibres

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

where do alpha-adrenoceptors occupy

A

smooth muscle cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

where do beta-adrenoceptors occupy

A

adipose tissue
skeletal muscle
liver
cardiac cells

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

role of cAMP in the activation of phosphorylase

A

adrenaline induced secondary messenger that leads to the activation of phosphorylase

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

what is the function of the N-terminus and c1 and c2 regions of adenyl-cyclase

A

important for regulation by Galpha-GTP Complex signalling in mammalian cells

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

which forms of adenylate cyclase are activated by calmodium/Ca2+ and inhibited by Ca2+

A

activated:
- III
- V
- VIII
inhibited:
- I
- VI

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

what does the GPCR-ligand stimulate

A

conversion of GDP to GDP at the Gα subunit

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

what do the GTP conversion stimulate

A

dissociation of Gα from the beta/gamma subunits

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

what stimulates adenylate cyclase

A

a dissociated Gα subunit

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

what does intrinsic or stimulated GTPase activity cause

A

return of Gα to resting state and association with beta/gamma subunits

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

structure of protein kinase A (PKA)

A

consists of 2 regulatory subunits - inactive form (R2-C2)
2 catalytic subunits - active form - (C2)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

what is allosteric activation

A

when cAMP activates PKA by dissociating the R subunits from the R2-C2 complex

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

what does the R-subunit of PKA contain

A

pseudosubstrate-sequence

40
Q

what does cAMP dependant PKA target and what does it lead to

A

phosphorylase kinase
leads to glycogenolysis

41
Q

what precisely causes the conformational change of phosphorylase kinase

A

phosphorylation of serine 14

42
Q

how are receptors desensitised to switch of GPCR and cAMP signalling

A

GPCR N-terminal is phosphorylated by beta-adrenergic receptor kinase

43
Q

what do phosphorylated GPCR N-terminal tails recruit and what do they do

A

beta-arrestin
attenuates heterotrimeric G-protein activation
induces receptor internalisation

44
Q

how is Gα deactivation achieved

A

intrinsic or GAP stimulated GTPase activity

45
Q

what does GTP hydrolysis cause

A

stops activation of downstream targets
causes re-association of Gα with beta/gamma subunits

46
Q

how is cAMP deactivation achieved

A

activation of phosphodiesterase (PDE)
hydrolysis of cAMP to generate AMP

47
Q

what do PKA phosphorylates signal to in terms of fatty acids

A

hormone sensitive lipase (HSL)
perilipin

48
Q

what is the function of HSL

A

leads to translocation to lipid droplet and its activation

49
Q

function of perilipin and what inhibits it

A

acts as a barrier to lipid hydrolysis
phosphorylation

50
Q

how does beta-adrenergic signalling stimulate increased heart rate and force
step 1

A

the Ca1.2 channel increases Ca2+ influx in response to depolarisation

51
Q

how does beta-adrenergic signalling stimulate increased heart rate and force
step 2

A

the ryanodine receptor (RYR) stimulated increased calcium induced calcium released from the sarcoplasmic reticulum
increased heart force

52
Q

function of phospholambam and what does it lead to

A

prevents it from inhibiting SERCA mediated Ca2+ uptake
enables faster relaxation for next contraction
faster HR

53
Q

what is a-kinase anchoring protein (AKAP)

A

contribute to spatial and selective restriction PKA signalling

54
Q

what does cholera toxin switch on

A

Gs-coupled proteins

55
Q

what switches off Gi-coupled protiens

A

pertussis toxin

56
Q

what adrenergic receptors does adrenaline act on for lipolysis

A

β3/α2 receptors in adipose

57
Q

what does Gαq activate

A

phospholipase C (PLC) to regulate downstream smooth muscle cell contraction

58
Q

Structure of phosphatidylinositol(4,5)bisphosphate (PtdIns(4,5)P2)

A

Favoured chair structure has 5 equatorial OH and 1 axial oh.
Consider a turtle with its head as the axial OH then the glycerol is connected to the right flipper which is position 1.

59
Q

what does α-1 adrenoceptors act as

A

act as GEF for Gαq
leads to PLC activation and Ptdlns4,5P2 hydrolysis
leads to contraction and vasoconstriction

60
Q

how is PLCβ1/3 activated

A

PLCβ1 - activated by Gαq
PLCβ3 - activated by β and gamma subunits

61
Q

how is PLCγ1 activated

A

Tyrosine phosphorylated receptor interacts with SH2 domain of PLCγ1. PLCγ1 is then tyrosine phosphorylated and activated

62
Q

GPCR activate PLC mediated hydrolysis of PtdIns(4,5)P2 to produce what

A

to generate two new second messengers Diacylglycerol (DAG) and Ins(1,4,5)P3

63
Q

features of lns(1,4,5)P3

A

water-soluble molecule and diffuses across the cytoplasm to the IP3 receptor which is found on the membrane of the endoplasmic reticulum

64
Q

features of lns(1,4,5)P3-receptor

A

ligand-gated ion channel that allows the influx of calcium cations upon activation
3 isoforms exist

65
Q

structure of lns(1,4,5)P3-receptor

A

made of a tetramer:
- N-terminal Ins(1,4,5)P3binding domain
- Coupling domain
- Transmembrane domain
- Gatekeeper domain

66
Q

how is Ins(1,4,5)P3-Receptor
activated

A

IP3 binds to the binding domain on the cytosolic face
leads to conformational changes
channel is opened
calcium influx

67
Q

what downstream target is activated in response to increase in diacylglycerol (DAG)

A

Protein Kinase C (PKC)

68
Q

what relieves psuedosubstrate inhibition

A

DAG and Ca2+ at the membrane induce conformational changes

69
Q

what is PKC regulated by and what is its function

A

receptor for activated C-kinase (RACK)
regulates downstream phosphorylation

70
Q

what is EPAC (exchange protein directly activated by cAMP)

A

EPAC is a guanine nucleotide exchange factor (GEF) that binds cAMP which induces a conformational change to activate its GEF activity

71
Q

which has a higher lower affinity for cAMP
PKA or EPAC and what does it mean

A

EPAC
only activated at high concentrations

72
Q

what is RAP

A

a small molecular weight G-protein
acts as a molecular switch to regulate cytoskeletal dynamics, cell adhesion and secretion

73
Q

what family does the insulin receptor belong to

A

tyrosine kinase receptor superfamily

74
Q

what does ligand induced dimerisation of tyrosine receptor induce

A

cross phosphorylation
increased kinase activity
further receptor tail phosphorylation

75
Q

purpose of the activation-loop phosphorylation

A

stabilises the active conformation of the insulin receptor tyrosine kinase (IRK)

76
Q

what is P85 and what does it lead to

A

a regulatory subunit of PI3K
contains an SH2 domain
when bound to the receptor PI3K becomes active
generates PIP3

77
Q

what does the SH2 domain of P85 also recruit

A

PLCγ to the phosphorylated receptor
activates PLCγ
generates DAG and IP3

78
Q

function of the SH2 domain of Grb2

A

mediates recruitment and subsequent activation of the RAS/MAPK pathway

79
Q

what does tyrosine phosphorylation lead to

A

receptor ubiquination and internalisation

80
Q

how is ubiquitin coupled to tyrosine phosphorylation

A

via the SH2 domain of casitas B-lineage lymphoma (Cbl protein)

81
Q

what is the agonist lipid secondary messenger

A

Ptdlns(3,4,5)P

82
Q

what is PTEN and what does it do

A

a tumour suppressant
removes the 3 phosphate from Ptdlns3,4,5P3

83
Q

what is SHIP1/2

A

a 5-phosphatase
removes the 5 phosphate from Ptdlns3,4,5P3

84
Q

what does SHIP generate

A

Ptdlns3,4P2
has messenger functions

85
Q

interaction of Class 1A p110 catalytic domain with p85 regulatory domain causes what

A

suppression of p110 subunit activity
prevents proteolytic degradation of p110
enables recruitment of holoenzyme to activated RTK receptor

86
Q

what enables the coupling of tyrosine kinase receptor to class 1A PI3K

A

the SH2 domain of p85 interaction with specific tyrosine phosphorylated receptor peptide

87
Q

what drives the synthesis of PIP3

A

SH2 mediated activation of PI3-kinase

88
Q

function of GRB2

A

is an adapter protein
DH2 domain binds to specific tyrosine phosphorylated residues on an RTK

89
Q

what does GRB2 recruit and how

A

recruits the SOS protein
via interaction with its SH3 domain with the proline-rich domain on the SOS protein

90
Q

what is SOS and what enhances it

A

guanine nucleotide exchange factor for RAS
activity is enhanced by interaction with the PH domain of Ptdlns4,5P2

91
Q

what leads to conformational changes in RAS and what does it allow

A

GTP exchange
enables reader interaction

92
Q

what does the binary switch action of RAS cause (in terms of regulation)

A

converts GTP binding into the regulation of protein phosphorylation driven by the RAF/MAP kinase pathway

93
Q

in terms of activation, what does the binary switch action of RAS cause

A

converts GTP binding into the activation of PI3K and PtdIns(3,4,5)P3 signalling

94
Q

what does deregulation of RAS signalling lead to

A

cell proliferation and tumours

95
Q

what specific mutations lead to RAS GTP accumulation

A

Gln61
Gly12

Biomed 2 (18 decks)

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