Signal Transduction Flashcards
1
Q
By which method of action can an agonist cause a conformational change in a receptor?
A
Lock & Key and Curvy grip
2
Q
Is competitive inhibition action altered by concentration of agonist
A
Yes, the agonist and competitive inhibitor compete to bind to the same site
3
Q
Is non-competitive inhibition action altered by concentration of agonist?
A
No, they bind to different sites; the non-competitive ligand binds to the allosteric site
4
Q
How quickly do ionotropic receptors produce a result?
A
milliseconds
5
Q
How quickly do metabotropic receptors produce a result?
A
seconds
6
Q
How quickly do kinase linked and nuclear receptors produce a result?
A
hours
7
Q
When receptors are turned on, what happens to the receptor itself, soon after?
A
the receptors are set to turn themselves off or inhibit themselves through a variety of mechanisms
8
Q
In a ligand channel, what does the ligand bind to?
A
the binding domain
9
Q
What is the binding domain of the receptor linked to?
A
A transmembrane pore
10
Q
What happens to the transmembrane pore when the binding domain is activated?
A
It un-kinks and opens the pore allowing ion passage
11
Q
Cys-loop receptors are ligand channels, what does their name derive from?
A
The highly conserved cysteine di-sulphide bond in the pore domain
12
Q
Which subunit is the binding domain found on?
A
Alpha
13
Q
Which subunit is the pore domain found on?
A
Delta
14
Q
Name two examples of cys-loop ligand channels
A
Nicotinic (for ACh) and GABAa receptor
15
Q
Name a GPCR
A
Rhodopsin
16
Q
What are the three main domains of rhodopsin?
A
transmembrane, extracellular and intracellular
17
Q
Which domain regulates the g-protein?
A
intracellular
18
Q
How does a G-protein become activated?
A
by converting GDP to GTP
19
Q
How do g-proteins self-deactivate?
A
GTPase converts GTP to GDP
20
Q
The release of GDP causes what to happen?
A
Beta-gamma and delta domain to dissociate
21
Q
Name 4 targets for delta domain once it has dissociated
A
RhoGEF, Phospholipase C, Adenylyl Cyclase and ion channels
22
Q
How many transmembrane domains are there in the rhodopsin class of gpcr?
A
7
23
Q
On which loop is the intracellular domain found?
A
third
24
Q
When does GPCR desensitisation occur?
A
Often just after the ligand has bound to it
25
What is heterologous GPCR desensitisation?
PKC and PKA inhibit g protein coupling
26
What is homologous GPCR desensitisation?
GRK phosphorylates the receptor causing the inhibition of G-alpha and facilitates Beta-arrestin
27
What is the action of beta-arrestin
to facilitate endocytosis of receptors and initiate recycling back to the membrane
28
What is the secondary function of beta-arrestin
As a signal transducer intracellularly
29
Are second messengers generally hydrophilic or hydrophobic?
hydrophobic
30
What does 2nd messenger G-alpha S increase?
cAMP
31
What does 2nd messenger G-alpha I decrease?
cAMP
32
Which receptors can release G-alpha S?
Beta Adreno, prostacyclin and prostaglandin E2
33
Which receptors can release G-alpha I?
Alpha 2 Adreno, chemokine and cannabinoids
34
What is a target of amplification?
Protein Kinase A (PKA)
35
Which toxin can activate G-alpha S?
Cholera
36
Which toxin can inhibit G-alpha I?
Pertussis
37
What do G-alpha S/I directly target?
Adenylyl Cyclase
38
What does adenylyl cyclase (AC) catalyse?
ATP conversion to cAMP
39
What does Phosphodiesterase (PDE) do to cAMP?
Degrades it to 5' AMP
40
How do types of PDE and AC differ?
Sequence, regulation, distribution and substrate specificity
41
cAMP can activate PKA, what can PKA do?
Inhibit cAMP
42
After activation, how long should you wait to see the maximum concentration of cAMP before it is self-inhibited?
2-10 minutes
43
What can Beta 2 (Adreno) linked cAMP rise cause?
Increased metabolism and glycogen
44
What can Beta 1 (Adreno) linked cAMP rise cause?
increased calcium channel activity in the heart
45
Prostacyclin IP and Beta 2 linked cAMP rise cause?
Phosphorylation of MCLK (smooth muscle relaxation)
46
What can Alpha 2 (Adreno) linked cAMP fall cause?
Inhibition of NT and insulin release and vascular contraction
47
What other effects of a fall in cAMP can occur?
K+ channels opening and cell hyperpolarisation
48
What are 3 main examples of G alpha Q receptors?
Muscarinic, Angiotensin and Alpha 1 Adreno
49
When activated, Phospholipase C (PLC) activates what?
PIP2
50
What does PIP2 activate?
IP3 and DAG
51
Can IP3 and DAG diffuse throughout the cell?
IP3 can but DAG is membrane bound
52
What does IP3 cause?
Release of intracellular Calcium
53
What does DAG cause?
Activation of Protein Kinase C (PKC)
54
After it has caused the release of Ca2+, what happens to IP3?
Phosphorylated to IP
55
After it has activated PKC, what happens to DAG?
Kinased to PA
56
What do IP and PA do?
Inhibit PIP2
57
What does an intracellular increase of Ca2+ cause?
migration of PKC to the membrane to be activated by DAG
58
What are 3 main examples of RhoGEF receptors?
Sphingosine 1-phosphate, lysophosphatidic acid and proteinase activted
59
What do RhoGEF do?
Facilitate GD/TP exchange at RhoA, activating ROCK
60
What can increased RhoGEF activity result in?
Smooth contraction, proliferation, angiogenesis and migration
61
What is the in Vivo half-life of NO?
2-5s
62
What does Nitric Oxide Synthase do?
Catalyses synthesis of NO
63
What is used up in the formation of NO?
L-arginine and O2
64
What is the rate-limiting step in NO synthesis?
NOS
65
Which forms of NOS are expressed constitutively?
Endothelial (eNOS) and Neuronal (nNOS)
66
Which form of NOS is not expressed constitutively?
Inducible (iNOS)
67
Which type of NOS produces more NO?
iNOS produces 1000x more
68
What does high blood pressure stress on endothelial cells cause?
AKT activation
69
What does AKT do?
Stimulate eNOS
70
Which receptor is involved in increasing Ca-Calmodulin?
Muscarinic
71
Which receptor is involved in increasing cAMP?
Beta Adenergic
72
What can increased PKA and Ca-Calmodulin cause?
eNOS stimulation
73
In neuronal tissues, what increases intracellular calcium?
Neurotransmitters
74
What does a neuronal increase of Ca/Ca-Calmodulin cause?
nNOS activation
75
Which particular receptor is involved in neuronal NT/Ca influx?
Glutamate
76
Does an increase in intracellular Ca2+ activate iNOS?
no
77
What activates iNOS?
Inflammation
78
What happens to NO in the presence of superoxides (O2-)?
Peroxynitrite is formed (ONOO-)
79
What can peroxynitrite do to pathogens?
Nitrosylate (and kill)
80
What is the overall function of eNOS?
Control regional BP, flow and platelet activity
81
What is the overall function of nNOS?
Control neurotransmission, LTP, Plasticity, Gastric emptying, Upper airway constriction and erections.
82
What can NO activate?
Guanylate Cyclase (GC)
83
What can GC do?
Convert GTP to cGMP
84
What effect does cGMP have on vascular muscle?
Relax it
85
What effect can Hypercholstermic induced reduction of NO cause?
Athergenesis
86
What can a lack of NO result in the formation of?
LDL (and thus arthersceloris)
87
What can LDL cause in terms of NO?
Decreased L-arginine uptake
88
How do statins reduce risk of atherosclerosis?
Decreasing LDL production
89
What (briefly) is angina?
Spasm of coronary artery
90
Statins stabilise eNOS mRNA, how does this reduce CVS risk?
Increases eNOS expression, decreases platelet activity and vasoconstriction
91
What effect does GTN have?
Mimics NO stimulation of Guanylate Cyclase
92
Which receptor does Sildenafil inhibit?
Phosphodiesterase V
93
What can sudden and large expressions of iNOS cause?
Septic shock
94
What is an inhibitor of iNOS?
Glucocorticoids
95
When is ADMA found in higher concentrations?
In CVD
96
What does ADMA do?
Inhibit eNOS
97
How can ADMA levels be reduced?
Exercise
98
What do Kinases do to proteins?
Take a Pi from ATP and phosphorylate the protein
99
What are the 3 main types of Kinase-Linked receptors?
Receptor Tyrosine Kinase (TRK), Serine/Threonine Kinase and Cytokine receptors (non-TRK)
100
How many transmembrane domains do RTK have?
one
101
In RTK, what is the N-terminus?
Binding domain
102
In RTK, what is the C-terminus?
Kinase domain
103
What are 4 examples of RTK?
Insulin receptor, PDGFR, EGFR and TrkA
104
What function are RTK generally associated with?
Growth and Development
105
What happens when RTK ligand binds to it?
It dimerises with another RTK
106
What does RTK dimerisation cause?
Tyrosine residue Autophorphorylation
107
What does tyrosine autophosphorylation cause?
It attracts proteins with an SH-2 domain
108
Do cells across the body have the same SH-2 domain protein?
No. The same ligand can cause different effects around the body due to differential expression of SH-2 domain proteins.
109
What is PDGFR?
Platelet-Derived Growth Factor Receptor
110
What are 3 examples of PDGFR-induced SH-2 proteins?
PLC-gamma, GAP and Phosphatase
111
Which cascade do most RTK activate?
RAS/MAPK
112
What are the MAPK sequentially acting proteins
MAPKKK, MAPKK and MAPK
113
What happens to MAPK in some cancers?
It can become defective
114
What happens as a result of defective MAPK signalling?
RAS drives oncogenesis as it is permanently bound to the cell membrane
115
The '-mab' suffix indicates what in a drug?
Antibody therapy
116
What is the main structural difference between RTK and Cytokine receptors?
Cytokine receptors have no Kinase/Enzymatic domain
117
Name 4 main Cytokine receptor types.
GM-CSF, Interferon-gamma, Growth Hormone and Interleukin I.
118
What are Cytokine receptors often associated with?
Immune and Haematopoietic functions
119
What is JAK/STAT?
Janus Kinase/ Signal Transducer & Activator of Transcription
120
When Cytokine receptors dimerise, what does JAK do?
It phosphorylates the tyrosine residue
121
What does JAK phosphorylation result in for STAT?
They are recruited and dimerised.
122
What happens to dimerised STAT?
They translocate to the nucleus
123
What are nuclear receptors?
Ligand Gated Transcription Factors
124
In addition to the C and N terminus, what domain do nuclear receptors have?
A core DNA binding and recognising domain
125
How are nuclear receptors activated?
Intracellular Ligands
126
When nuclear receptors are activated, what happens to them?
They dimerise and bind to the Hormone Response Element of DNA (HRE)
127
Name 4 main types of nuclear receptors.
Oestrogen receptors, Glucocorticoid receptors, Vitamin D receptor and Free Fatty Acids
128
What are the three main classes of nuclear receptors?
Class 1, 2 and Hybrid
129
What are class 1 nuclear receptors?
Lipid/Retinoid receptors
130
What are class 2 nuclear receptors?
Steroid receptors
131
What are hybrid nuclear receptors
Endocrine receptors
132
What are Orphan GPCR
GPCR or nuclear receptors of which the ligand has not been identified
