Strand 3 - Cell signalling Flashcards

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1
Q

what is the first stage of signal transduction? (hint: involves the first messenger)

A

an extracellular signal molecule activates a membrane receptor

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2
Q

what is the second stage of signal transduction

A

intracellular molecules are transduced via a certain pathway

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3
Q

what is the third stage of signal transduction?

A

activating a cellular response

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4
Q

give an example of an amine which is a first messenger

A

adrenaline

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5
Q

give an example of a peptide/protein that is a first messenger

A

angiotensin 2

insulin

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6
Q

give an example of a ligand gated ion channel (hint: think nervous system)

A

nicotinic ach receptor

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7
Q

which subunits make up the nicotinic ach receptor

A

2 alpha
1 beta
1 delta
1 epsilon

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8
Q

which ion is GABA A selective for?

A

Cl-

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9
Q

which two substances activate GABA A receptors?

A

alcohol and anaesthetics

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10
Q

name a muscarinic receptor which activates a potassium channel

A

GABA B

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11
Q

what are metabotropic receptors connected to? and what does it do?

A

connected to a G protein

opens ion channels

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12
Q

what do ionotropic receptors form in the membrane? what does this allow?

A

a pore

allows an ion to pass into a cell

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13
Q

how many chains are G proteins made of? what are they?

A

3

alpha, beta, gamma

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14
Q

the alpha subunit of a G protein has a …… binding site that binds…….

A

guanine

GTP/GDP

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15
Q

does alpha GDP have a high affinity for the resting B-gamma or the active one?

A

resting

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16
Q

the alpha subunit of a G protein hydrolyses GTP. what molecule does this activate?

A

adenyl cyclase

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17
Q

in an inactive PKA molecule are the subunits bound together or not?

does the R subunit suppress the activity of the C subunit

A

yes and yes

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18
Q

the R subunits in PKA have how many binding sites for cAMP?

A

2

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18
Q

which 2 chains does PKA have?

A

catalytic and regulatory

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18
Q

What does PKA catalyse the transfer of to serine or threonines on substrates?

A

ATP

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19
Q

which cellular response is activated by cAMP in the kidney collecting duct?

A

water retention (vasopressin)

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20
Q

which cellular response is activated by cAMP in the smooth/cardiac muscle?

A

relaxation of muscle / increase of heart rate (adrenaline)

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20
Q

which cellular response is activated by cAMP in the colonic epithelium?

A

promotion of fluid/electrolyte secretion

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21
Q

which cellular response is activated by cAMP in the pancreas?

A

promotion of the release of glucose in the blood (glucagon)

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22
Q

what is cAMP hydrolysed by?

A

phosphodiesterase

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23
Q

phosphodiesterases are inhibited by which substance?

A

caffeine

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24
Q

what does Beta adrenoreceptor kinase do to a beta adrenoreceptor?
what effect does this have on the affinity it has for adrenaline?

A

phosphorylates it

reduces affinity for adrenaline

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25
Q

what does the stimulatory alpha subnit stimulate in a G protein?

A

adenyl cyclase

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26
Q

what does the inhibitory alpha subnit inhibit in a G protein?

A

adenyl cyclase

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27
Q

which alpha subunit of a G protein does the cholera toxin act on?

A

the alpha stimulatory subunit

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28
Q

when cholera toxin binds to the alpha stimulatory subunit of a G protein what does it cause to happen to ADP?

what does this cause to happen to the alpha subunit in turn?

A

ADP ribosylation

hydrolysis of GTP = constant activation of alpha subunit

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29
Q

in the colon, the cholera toxin activates what?

what does this cause in turn to be excreted from the body?

A

PKA dependent Cl- channels

secretory diarhhoea

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29
Q

which alpha subunit of a G protein does pertussis toxin act on? and what does it prevent?

what does this increase therefore ?

A

the inhibitory alpha subunit - prevents activation by receptors and increases cAMP

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30
Q

what does pertussis toxin lead to in the airways?

A

whooping cough

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31
Q

which unique subunit do Gq proteins contain?

A

alpha q-11

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32
Q

what do Gq proteins allow hormones to do?

A

activate the amplifier enzyme phospholipase C

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33
Q

What does phospholipase C cleave to produce IP3 and DAG?

A

PIP 2

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34
Q

what does IP3 stimulate the release of from the ER?

A

Calcium

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35
Q

what does DAG recruit when it remains in the membrane?

A

Protein kinase C

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36
Q

how many Ca2+ does each calmodulin bind to ?

A

4

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37
Q

what doe the Ca2+/CaM complex activate?

A

CaM kinases

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38
Q

What do CaM kinases cause the contraction of in the body?

A

smooth muscle

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39
Q

which 2 residues do CaM kinases phosphorylate?

A

serine and threonine

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40
Q

What can PKCs potentiate the effect of which in turn mediates the desensitization via cf Beta- ARK?

A

IP3

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41
Q

What does alpha 1 adrenoreceptor cause the constriction of?

A

vascular smooth muscle

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42
Q

Which G protein causes blood pressure to increase?

A

Gq-PLC-IP3-CaMK

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43
Q

Which G protein causes blood pressure to decrease via vasodilation?

A

Gs-cAMP-PKA

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44
Q

which 3 subtypes (out of 1-5) of muscarinic receptors are Gq coupled stimulatory?

A

1, 3, 5

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45
Q

**which 2 subtypes (out of 1 to 5) of muscarinic receptors are Gi protein coupled inhibitory?

A

2 and 4

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46
Q

which 2 receptors are coupled with a Gi protein? (hint: one adrenergic and one muscarinic)

A

a2 adrenergic
M2 muscarinic

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47
Q

what is the function of the guanyl cyclase domains on guanyl cyclase receptors?

A

to convert GTP to cGMP

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48
Q

give an example of a response from an activated guanyl cyclase receptor?

A

vasodilation/ relaxation of vascular smooth muscle

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49
Q

what is the function of the Ser-Thr domains on Ser-Thr kinase receptors?

A

phosphorylation of target proteins

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50
Q

give an example of a response elicited by an activated ser-thr kinase receptor?

A

cell proliferation

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51
Q

what 2 things do tyrosine kinase domains in TKRs phosphorylate?

A

themselves and other proteins

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52
Q

give an example of a response caused by an activated tyrosine kinase receptor?

A

insulin mediated glucose uptake / storage in liver or muscles

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53
Q

tyrosine kinase associated receptors do not contain which type of domain?

A

kinase domains

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54
Q

what does the dimerization of tyrosine kinase associated receptors cause the activation of? Give an example

A

associated tyr kinases such as JAK2

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55
Q

give an example of a cellular response elicited by the activation of a tyrosine kinase associated response

A

EPO mediated increased production of blood cells

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56
Q

what do the tyrosine phosphatase domains dephosphorylate in tyrosine phosphatase receptors?

A

target proteins

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57
Q

give an example of a response elicited by the dephosphorylation of target proteins by tyrosine phosphatases

A

maturation of lymphocytes

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58
Q

what is glucose stored as in the liver and muscles?

A

glycogen

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59
Q

after a meal what happens to glucose absorption?

A

increases

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60
Q

what concentration is circulating glucose normally?

A

5mM

61
Q

what does insulin promote the storage of? and as what?

A

glucose

stored as glycogen

62
Q

what do the alpha cells of the pancreas produce?

A

glucagon

63
Q

what do the beta cells of the pancreas produce? (2 things)

A

insulin and amylin

64
Q

what do the gamma cells of the pancreas produce?

A

somatostatin

65
Q

what is pro insulin activated by?

A

prohormone convertase 1 and 2

66
Q

insulin is made up of ….. polypetide chains held together by …… bonds?

A

2

disulphide

67
Q

what is insulin stored in within B cells?

A

secretory granules

68
Q

at what concentration of glucose is insulin at its highest concentration?

A

9 mM

69
Q

Which GLUT transporter is expressed by B cells and is always open?

A

GLUT 2

70
Q

in B cells, what is glucose phosphorylated to?

what is it phosphorylated by to generate ATP?

A

glucose - 6 - phosphate

by glucokinase

71
Q

When is the Vm depolarised in B cells?

A

when glucose concentration is HIGH

72
Q

when the Vm is depolarised in B cells which ion channel is open and which is closed?

A

K+ is closed

Ca2+ is open

73
Q

into which vein is insulin released from the pancreas?

A

hepatic portal vein

74
Q

in insulin release, P13K activation causes the activation of which protein kinase?

which GLUT channel does this then cause the translocation of to the PM?

A

PKB

GLUT 4

75
Q

hepatic glucose uptake depends primarily on which GLUT channel?

A

GLUT- 4

76
Q

if glycogen reserves are full, what is glucose metabolised to via oxidation?

A

fatty acids

77
Q

when do the alpha cells of the pancreas secrete glucagon?

A

when blood glucose levels are low

78
Q

what event can trigger glucagon release?

A

hypoglycaemia

79
Q

during exercise, how does glucagon allow the skeletal muscle to indirectly metabolise glucose?

why is this necessary?

A

causes the translocation of GLUT-4 to the plasma membrane of skeletal muscle cells = GLUCOSE UPTAKE

because skeletal muscles do not have glucose receptors present on their PM

80
Q

which 2 hormones can promote glycogenolysis?

A

glucagon and adrenaline

81
Q

what do high levels of glucagon cause the release of from adipose tissue?

A

fatty acids

82
Q

when glycogen has been depleted, what does glucagon stimulate the formation of?

what is this process known as

A

glucose

gluconeogenesis

83
Q

in gluconeogenesis, what 2 things is glucose formed from?

A

lipids and amino acids

84
Q

what is diabetes mellitus defined as?

A

the inability to regulate blood glucose

85
Q

diabetes mellitus means blood glucose levels are consistently above what concentration?

A

7mM

86
Q

what is the ‘safe’ range of blood glucose?

A

3-7mM

87
Q

Type 1 diabetes is the failure to….., resulting in high levels of blood……

A

secrete insulin

glucose

88
Q

type 2 diabetes is caused by what?

this results in high levels of…… in the blood?

A

resistance to insulin

glucose

89
Q

type 1 diabetes is an autoimmune disease, mediated by which type of T cells?

A

CD8 cytotoxic T cells

90
Q

which cells are destroyed in type 1 diabetes?

A

B cells

91
Q

In type 1 diabetes mutations in caucasians, what is Asp57 substituted to in the HLA-DQ beta 1 chain?

( 3 AAs)

A

valine, alanine or serine

92
Q

Which haplotypes are associated with type 1 diabetes?

A

HLA-DR3, HLA-DR4

93
Q

In type 1 diabetes, why is the absorption capacity of the PCT overwhelmed, causing the increase of urine flow and therefore dehydration?

A

too high of a glucose concentration enters the glomerulus

94
Q

why is weight loss associated with type 1 diabetes when no insulin is being made?

A

no insulin made = glucose not used by tissues = use fatty acids instead

95
Q

when does ketoacidosis occur in type 1 diabetes, resulting in a coma or death?

A

in the presence of too many ketone bodies causing the decrease of pH = metabolic acidosis

96
Q

what is a problem caused by continuous insulin injection into one site on the body?

A

fat deposition or lipohypertrophy

97
Q

why do patients with type 1 diabetes need to change their insulin injection site often?

A

they have poor glycaemic control and therefore unpredictable insulin absorption (can get hyper/hypoglycaemic easily)

98
Q

which combination of insulin forms would be used routinely to control glycaemia?

A

soluble insulin and glargine

99
Q

which 2 events follow the hyperglycaemia stage in type 2 diabetes?

A

hyperinsulinaemia

Beta cell failure

100
Q

which 2 molecules can lead to insulin resistance in type 2 diabetes?

A

IL-1 and DAG

101
Q

Which of 2 drugs work by improving insulin secretion from the Beta cells of the pancreas?

A

gliclazide and GLP-1 agonists

102
Q

what is soluble insulin used to treat?

is it rapid or slow onset?

A

hyperglycaemic emergencies only

rapid onset

103
Q

give an example of a long acting insulin drug?

A

insulin zinc suspension

104
Q

give an example of a very rapid and very short lived insulin analogue drug which is taken by diabetic patients before a meal?

A

insulin lispro

105
Q

which slow acting, insulin analogue is taken by diabetic patients before a meal IN COMBINATION with a short acting form?

A

insulin detemir

106
Q

give an example of an INSULIN ANALOGUE which is LONG ACTING

A

insulin glargine

107
Q

which insulin drug targets the autoimmune reaction in type 1 diabetes?

A

teplizumab

108
Q

which 2 drugs are used to routinely control glycaemia?

A

lispro and detemir

109
Q

in type 2 diabetes, insulin resistance is caused by what?

A

the decrease of glucose uptake

110
Q

what is hyperinsulinemia, in relation to the beta cells and insulin demand? (type 2 diabetes)

what does it lead to the decrease of?

A

the failure of the beta cells of pancreas to keep up with the peripheral demand of insulin

leads to the decrease of insulin secretion

111
Q

what causes insulin resistance in liver and muscle in type 2 diabetes?

A

free fatty acids

112
Q

when in excess, free fatty acids in type 2 diabetes are transformed to which second messenger?

A

DAG

113
Q

DAG activates PKC. What does PKC phosphorylate on Ser residues which in turn attenuates the insulin receptor signal?

A

IRS-1

114
Q

the expression of what enzyme is reduced in obesity (type 2 diabetes)?

A

adiponectin

115
Q

what does the enzyme adiponectin improve by activating AMPK?

A

insulin sensitivity

116
Q

what does the enzyme AMPK promote in liver and muscle?

A

lipolysis

117
Q

which drug are AMPK activators used in for type 2 diabetes?

A

metformin

118
Q

what is the nuclear receptor involved in adipocyte differentiation?

A

PPAR gamma

119
Q

what does the receptor PPARy promote the secretion of?

A

anti-hyperglycaemic adipokines

120
Q

which two interleukins are produced by adipocytes to attract macrophages to fat deposits?

A

IL-6 and IL-1

121
Q

Which drug is an agonist for the PPARy receptor in diabetes type 2?

A

Pioglitazone

122
Q

which drug can suppress glucose release from the liver, activate AMPK and increase lipolysis in liver?

A

metformin

123
Q

give an example of a sulphonylurea drug which bind to receptors expressed on beta cell membranes (type 2 diabetes)

A

Gliclazide

124
Q

which ion channel does gliclazide block in beta cells?

what does this cause the beta cell to do?

A

K+ channels

causes depolarization and opening of Ca2+ channels and insulin secretion

125
Q

What can B3 agonists control in fat cells?

A

lipolysis

126
Q

what do alpha 2 adrenoreceptor antagonists increase the secretion of? (type 2 diabetes treatment)

A

insulin

127
Q

what do GLP-1 receptor agonists cause in beta cells?

A

increase insulin secretion from beta cells

128
Q

what effect do SGLT-2 inhibitors have on the excretion of glucose in urine? what does this induce?

A

increase it and induce ketogenesis

129
Q

what are some long term disease consequences of type 2 diabetes?

A

retinopathy, nephropathy, Coronary Artery Diseases

130
Q

what does type 2 diabetes generate which cause damage to blood vessels? (2 things)

A

reactive oxygen species and AGEs

131
Q

what do AGEs cross link with in type 2 diabetes causing inflammation and blood vessel damage?

A

collagen

132
Q

which domain of NF-KB encodes the DNA binding and dimerization functions?

A

the rel homology domain (RHD)

133
Q

what is the precursor protein for p50?

A

p105

134
Q

what is the precursor protein for p52?

A

p100

135
Q

is p50 part of the canonical or non-canonical p53 pathway?

A

canonical

136
Q

name physiological 4 events that activate NF-KB

A

hypoxia, DNA damage, infection, physical stress

137
Q

which 2 proteins involved in NF-KB signalling have regulatory functions but no catalytic activity?

A

IKB-alpha and IKK-gamma (NEMO)

138
Q

p105 and p100 in the NF-KB family have ankyrin repeats in which terminals?

A

C terminals

139
Q

in the non canonical p53 pathway, what does NIK kinase phosphorylate?

A

IKK alpha

140
Q

in the non-canonical p53 pathway, the precursor p52 associates with what?

A

Rel-B

141
Q

give examples of cellular events which NF-KB regulates?

A

cell death
cell proliferation
inflammation
angiogenesis
tumour metastasis
cell survival

142
Q

when NF-KB control is lost in cancerous cells, the cells become abherrantly …… instead of cytoplasmic

A

nuclear

143
Q

the N terminal domain of p53 contains which two domains that are involved in apoptosis regulation?

A

sub-transactivation and a proline rich domain

144
Q

in p53, what does the core domain bind to?

A

DNA sequences

145
Q

in p53, which domain is contained within the C terminal domain?

A

tetramerization domain

146
Q

does p53 suppress or promote tumour activity?

A

suppress

147
Q

which molecule keeps p53 inactive?

A

Mdm2

148
Q

does NF-KB promote or suppress cell survival?

A

promote

149
Q

in cancer cells, p53 is ….. and NF-KB is abherrant

A

mutated

150
Q

which cyclin can p53 repress?

A

D1

151
Q

which molecule can induce senescence in a p53 dependent manner in the crosstalk pathway?

A

EZH2

152
Q

in primary B cell chronic lymphocytic leukemia (CLL) cells, EZH2 expression is induced upon the stimulation of which CD ligand?

A

CD40L

153
Q

Via EZH2 regulation, which 2 subunits of p53 can antagonize p53 mediated cell senescence?

A

p52 and RelB

154
Q

regarding NF-KB and p53 crosstalks, which situation is most likely to happen in cancer cells? (hint: think antagonism

A

NF-KB antagonizes p53 functions