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Trinity Term 1 > Hormonal signalling > Flashcards

Hormonal signalling Flashcards

1
Q

Describe some general themes for signal transduction

A
  • specificity
  • coordination of multiple events
  • amplification
  • integration with other pathways
  • processing
  • sub-cellular localisation
  • speed
  • duration
  • tissue localisation
  • cost of machinery and metabolism
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2
Q

Describe an all-or-none curve

A

looks like tan

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3
Q

Describe a hyperbolic curve

A

the first half of a parabola

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4
Q

Describe contact-dependent pathways

A
  • developmental
  • signalling cell delivers membrane-bound signal molecule to target cell
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5
Q

Describe paracrine pathways

A
  • spatially localised
  • diffusible signal
  • local mediators
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6
Q

Describe endocrine pathways

A
  • steroid hormones
  • peptide hormones
  • travel in bloodstream to receptors on target cells
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7
Q

Describe synaptic pathways

A
  • neuronal: long distance, fast
  • from cell body along axons
  • neurotransmitters diffuse across synapses to target cells
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8
Q

Describe signalling via lipid soluble steroid hormones - the basics

A
  • diffuse across PM and activate members of the intracellular receptor superfamily
  • persist for hours/days
  • mediate long-term responses
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9
Q

Describe steroid hormones

A
  • small, hydrophobic molecules
  • transported in the blood
  • often associated with carrier proteins
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10
Q

List some steroid hormones

A
  • cortisol
  • estradiol
  • testosteron
  • retinoic acid
  • thyroxine
  • vitamin D3
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11
Q

Describe signalling via lipid soluble steroid hormones - the specifics

A
  • attached to carrier protein in blood
  • diffuse into cells
  • bind to steroid receptor binding element
  • releases inhibitory protein from intracellular receptor
  • moves into nucleus
  • activate gene regulatory proteins
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12
Q

Give the structure of a steroid hormone

A
  • COOH
  • ligand binding domain
  • inhibitory proteins
  • DNA-binding domain
  • transcription-activating domain
  • co-activator binding proteins
  • H2N
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13
Q

List the three classes of cell surface receptor

A
  • enzyme-linked receptors
  • G-protein coupled receptors
  • ion channel receptors
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14
Q

Describe enzyme-linked receptors

A
  • inactive catalytic domain binds to dimeric signal molecule to form active catalytic domain
  • OR signal molecule binds to receptor to form an activated, associated enzyme
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15
Q

Describe G-protein coupled receptors

A
  • inactive receptor followed by an inactive protein, followed by an inactive enzyme
  • signal molecule binds to create an activated receptor and G protein
  • creates activated enzyme
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16
Q

Describe ion channel receptors

A

ions bind to signal molecule to travel through the PM

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17
Q

Describe signalling via enzyme-linked cell-surface receptors

A
  • enzyme-linked receptors are catalytically active or associate with catalytic subunits
  • most are single-pass membrane proteins
  • often involved in development, activating cell division and growth
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18
Q

Describe RTKs functionally

A
  • Receptor tyrosine kinases
  • assemble as dimers on binding the target ligand and autophosphorylate their cytoplasmic tails
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19
Q

Describe TGF-Beta

A
  • growth factor
  • activates serine/threonine receptor kinases
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20
Q

Describe RTKs morphologically

A
  • cystine-rich domains
  • tyrosine kinase domains
  • EGF receptors
  • insulin, IGF1 receptors
  • NGF receptors
  • PDGF, MCSF receptors
  • FGF receptors
  • immunoglobin-like domains
  • VEGF receptor with kinase insert region
  • Eph receptor with fibronectin-type-III-like domain
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21
Q

Describe the binding of a ligand to the RTK

A
  • leads to receptor dimerisation
  • initiates tyrosine auto-phosphorylation
  • adapter proteins bind to phospho-tyrosine through SH2 domains
  • guanine exchange factors bind to SH3 domains on the adapter protein
  • GEF proteins activate small GTPases by catalysing exchange of GDP for GTP
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22
Q

Give an example of an adapter protein in RTK-ligand binding

A

GRB2

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23
Q

Give an example of a guanine-exchange factor

A

SOS

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24
Q

Give an example of a small GTPase

A

Ras

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25
What does activated Ras do?
- released - binds to Raf
26
Raf
- a serine/threonine kinase - can initiate a MAPK cascade
27
MAP
mitogen-activated protein
28
MAPK
- mitogen-activated protein kinase - the terminal enzyme in a three-kinase cascade - phosphorylates and activates transcription factors - is phosphorylated by MAPKK on two sites
29
MAPKK
- MAPK kinase - is phosphorylated by MAPKKK on two sites
30
MAPKKK
MAPKK Kinase
31
List some signals acting via RTKs
- EGF - insulin - IGF1 - NGF - PDGF - MCSF - FGF - VEGF - ephrin
32
EGF
- epidermal growth factor - EGF receptors - stimulates cell survival, growth, proliferation, or differentiation of various cell types - acts as inductive signal in development
33
Insulin
- insulin receptor - stimulates carbohydrate utilisation and protein synthesis
34
IGF1
- IGF receptor-1 - stimulates cell growth and survival in many cell types
35
NGF
- nerve growth factor - Trk receptors - stimulates survival and growth of some neurones
36
PDGF
- PDGF receptors - stimulates survival, growth, proliferation and migration of various cell types
37
MCSF
- macrophage-colony-stimulating factor - MCSF receptor - stimulates monocyte/macrophage proliferation and differentiation
38
FGF
- fibroblast growth factor - FGF receptors - stimulates proliferation of various cell types - inhibits differentiation of some precursor cells - acts as inductive signal in development
39
VEGF
- vascular endothelial growth factor - VEGF receptors - stimulates angiogenesis
40
Ephrin
- Eph receptors - stimulates angiogenesis - guides cell and axon migration
41
Describe G-protein coupled receptors with respect to the cell membrane
- extracellular signal acts as first messenger - receptor - transducer with G-protein attached to GTP - amplifier region - intracellular signal acts as second messenger
42
Describe the fundamentals of the G-protein coupled receptors
- >800 - 4% of the total human genome - major drug targets
43
Describe the 7-Membrane Spanning Domain G-protein receptors
- G protein-linked receptors have 7 membrane spanning alpha-helices - N-terminus and extracellular cytoplasmic loops bind the ligand - large cytoplasmic loop interacts with G-proteins
44
Describe coupling via trimeric G-proteins
- ligand binds to receptor - The β-gamma subunits can also initiate signal transduction - receptor undergoes conformational change - G-protein binds to receptor and exchanges GDP for GTP - GTP-alpha-subunit dissociates and binds to target enzyme - target enzyme activated - bound GTP hydrolysed and -subunit dissociates
45
Describe the GDP protein before coupling
- inactive - trimeric - with alpha, beta and gamma subunits
46
Describe adrenaline (epinephrine) action
- triggers tissue-specific responses via cAMP - beta-adrenergic receptors are coupled to adenylate cyclase by G-proteins
47
Describe adrenaline
- epinephrine - synthesised in adrenal medulla and released into bloodstream in response to stress - binds to beta-adrenergic receptors on the surface of muscle, liver and adipose cells
48
cAMP
triggers glycogen breakdown via a kinase cascade
49
Describe the glycogen breakdown kinase cascade
- PKA dissociates from cAMP - phosphorylated by phosphorylase kinase (ATP -> ADP and Pi) - phosphorylated by glycogen kinase - glycogen converted to glucose 1-phosphate
50
Describe feedback loops that desensitise beta-adrenergic receptors
- GTP transferred from beta-adrenergic receptors to adenylate cyclase - reacts with ATP and cAMP to produce PKA - inactivated by phosphorylation
51
List some hormone-induced cell responses mediated by cAMP
- thyroid - adrenal cortex - ovary - muscle - bone - heart - liver - kidney - fat
52
Describe the thyroid gland
- TSH - thyroid hormone synthesis and secretion
53
TSH
thyroid-stimulating hormone
54
Adrenal cortex
- ACTH - cortisol secretion
55
ACTH
adrenocorticotrophic hormone
56
Describe the ovary
- LH - progesterone secretion
57
LH
luteinising hormone
58
Describe the muscle
- adrenaline - glycogen breakdown
59
Describe the bone
- parathormone - bone resorption
60
Heart
- adrenaline - increase in heart rate and force of contraction
61
Liver
- glucagon - glycogen breakdown
62
Kidney
- vasopressin - water reabsorption
63
Fat
- adrenaline, ACTH, glucagon, TSH - triglyceride breakdown
64
Describe the inositol signalling pathway
- PI is phosphorylated to PIP, which is phosphorylated to PIP2 - passes through G-coupled PLC using GTP, across DAG to PKC - GTP produces InsP3 which binds to ER to secrete calcium, which migrates to PKC on PM - sets up positive feedback loop of calcium - SOCE achieved by calcium influx through ORA1 (attached to STIM1) delivered to SERCA in ER membrane, that transports back to calcium pump
65
List some of the roles of the IP3/Ca2+ signalling pathway
- metabolism - contraction - fluid secretion - neuronal synaptic plasticity - aggregation - ion channel opening - aldosterone secretion - differentiation - proliferation - exocytosis
66
Describe the IP3/Ca2+ signalling pathway in metabolism
liver cells
67
Describe the IP3/Ca2+ signalling pathway in contraction
- ventricular cells - atrial cells - smooth muscle - mesangial cells
68
Describe the IP3/Ca2+ signalling pathway in fluid secretion
- intestinal cells - parietal cells - pancreas - salivary glands - sweat glands
69
Describe the IP3/Ca2+ signalling pathway in neuronal synaptic plasticity
- purkinje neurones - hippocampal neurones
70
Describe the IP3/Ca2+ signalling pathway in aggregation
blood platelets
71
Describe the IP3/Ca2+ signalling pathway in ion channel opening
- astrocytes - T cells
72
Describe the IP3/Ca2+ signalling pathway in aldosterone secretion
glomerulosa cell
73
Describe the IP3/Ca2+ signalling pathway in differentiation
- osteoblasts - brown fat cells
74
Describe the IP3/Ca2+ signalling pathway in proliferation
- T cells - mesangial cells - smooth muscles - brown fat cells
75
Describe the IP3/Ca2+ signalling pathway in exocytosis
- b-Cells - L Cells - mast cells - macrophages - parathyroid glands - astrocytes - renin-producing granular cells
76
Describe the imaging of Ca2+-dynamics
- in C. elegans pharyngeal muscle - using cameleon 2.1 (transgenic probes for Ca2+)
77
Describe the role of phosphatidyl inositols as membrane scaffolds
- PIP - PI(4)P - PI(4,5)P2 - PI(3,4,5)P3 - phosphorylation by PI 3-kinase - can interact with cytoskeleton
78
What links PKA, CaM-kinase, PKC and MAPK
they are transcription regulators
79
Summarise GCPR pathway 1
- G protein - adenylyl cyclase - cyclic AMP - PKA - protein targeting/transcriptional regulation
80
Summarise GCPR pathway 2
- G protein - phospholipase C - IP3 - Ca2+ - calmodulin - CaM-kinase - protein targeting/transcriptional regulation
81
Summarise GCPR pathway 3
- G protein - phospholipase C - diacylglycerol - PKC - protein targeting/transcriptional regulation
82
Summarise RTK pathway 1
- phospholipase C - diacylglycerol - PKC - protein targeting/transcriptional regulation
83
Summarise RTK pathway 2
- Grb2 - Ras-GEF (Sos) - Ras - MAPKKK - MAPKK - MAPK - protein targeting/transcriptional regulation
84
Summarise RTK pathway 3
- PI 3-kinase - PI(3,4,5)P3 - (PDKT) - Akt kinase - protein targeting/transcriptional regulation
85
Summarise RTK pathway 4
- Grb2 - Ras-GEF (Sos) - Ras - PI 3-kinase - PI(3,4,5)P3 - (PDKT) - Akt kinase - protein targeting/transcriptional regulation
86
Describe the analysis of downstream signalling in multiple MAPK pathways
- DNA microarray with >97% of known or predicted genes from Saccharomyces cerevisiae - make green fluorescently labelled probes from cDNA library of normal cells - make red fluorescently labelled probes from cDNA library of cells treated with mating pheromome - apply probes to array and measure the red/green ratio - red = upregulated after pheromone, green=down regulated
87
Describe the cluster analysis of gene behaviour in yeast
- >200 gene transcripts found to increase in abundance - >200 decrease in abundance - 383 genes changed by >3 fold
88
Describe the testing of the pheromone hypothesis using mutants
- genome-wide transcript profiling repeated in different mutant backgrounds - deletion in ste2 abolishes the entire pheromone response - deletion in far1 does not affect induction of pheromone genes, but abolishes repression of cell cycle genes
89
ste2
pheromone receptor
90
far1
cdk inhibitor
91
Describe the acetylcholine receptor
- nAChR - archetypal pentameric ligand gated channel (alpha, alpha, beta, gamma, delta) - charges above and below the pore confer specificity for cations - alpha-subunits have binding sites for ACh and show cooperativity - Na+ is the main ion transported as it is far from equilibrium
92
Describe GABA and glycine receptors
- pentameric channels permeable to chloride ions - inhibit generation of an action potential by maintaining membrane hyperpolarisation - activated by benzodiazepines and barbiturates - inhibited by strychnine.
93
GABA
gamma-amino butyric acid
94
benzodiazepines
valium
95
Describe ionotropic glutamate receptors
- NMDA receptors - AMPA receptors
96
Describe NMDA receptors
- permeable to Ca2+ - promote depolarisation - blocked by Mg2+ until ejected by depolarisation
97
NMDA
N-methyl-D-aspartate
98
Describe AMPA receptors
- permeable to Na+ - promote depolarisation
99
AMPA
α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid
100
Describe metabotropic glutamate receptors
- glutamate receptors initiate a G-protein cascade that activates adenylate cyclase and PKA - Na+ channels activated by phosphorylation (by PKA)
101
Summarise the G protein cascade
- GDP to GTP - GTP binds adenylate cyclase - ATP to produce cAMP - releases pKA - goes to membrane receptor
102
Describe 5-HT receptors activate channels directly, or via the IP3 and cAMP pathways
103
5-HT
- 5-hydroxytryptamine - serotonin

Trinity Term 1 (38 decks)

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