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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
Q

What does activated Ras do?

A
  • released
  • binds to Raf
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26
Q

Raf

A
  • a serine/threonine kinase
  • can initiate a MAPK cascade
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27
Q

MAP

A

mitogen-activated protein

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28
Q

MAPK

A
  • mitogen-activated protein kinase
  • the terminal enzyme in a three-kinase cascade
  • phosphorylates and activates transcription factors
  • is phosphorylated by MAPKK on two sites
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29
Q

MAPKK

A
  • MAPK kinase
  • is phosphorylated by MAPKKK on two sites
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30
Q

MAPKKK

A

MAPKK Kinase

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31
Q

List some signals acting via RTKs

A
  • EGF
  • insulin
  • IGF1
  • NGF
  • PDGF
  • MCSF
  • FGF
  • VEGF
  • ephrin
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32
Q

EGF

A
  • epidermal growth factor
  • EGF receptors
  • stimulates cell survival, growth, proliferation, or differentiation of various cell types
  • acts as inductive signal in development
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33
Q

Insulin

A
  • insulin receptor
  • stimulates carbohydrate utilisation and protein synthesis
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34
Q

IGF1

A
  • IGF receptor-1
  • stimulates cell growth and survival in many cell types
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35
Q

NGF

A
  • nerve growth factor
  • Trk receptors
  • stimulates survival and growth of some neurones
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36
Q

PDGF

A
  • PDGF receptors
  • stimulates survival, growth, proliferation and migration of various cell types
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37
Q

MCSF

A
  • macrophage-colony-stimulating factor
  • MCSF receptor
  • stimulates monocyte/macrophage proliferation and differentiation
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38
Q

FGF

A
  • fibroblast growth factor
  • FGF receptors
  • stimulates proliferation of various cell types
  • inhibits differentiation of some precursor cells
  • acts as inductive signal in development
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39
Q

VEGF

A
  • vascular endothelial growth factor
  • VEGF receptors
  • stimulates angiogenesis
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40
Q

Ephrin

A
  • Eph receptors
  • stimulates angiogenesis
  • guides cell and axon migration
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41
Q

Describe G-protein coupled receptors with respect to the cell membrane

A
  • extracellular signal acts as first messenger
  • receptor
  • transducer with G-protein attached to GTP
  • amplifier region
  • intracellular signal acts as second messenger
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42
Q

Describe the fundamentals of the G-protein coupled receptors

A
  • > 800
  • 4% of the total human genome
  • major drug targets
43
Q

Describe the 7-Membrane Spanning Domain G-protein receptors

A
  • 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
Q

Describe coupling via trimeric G-proteins

A
  • 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
Q

Describe the GDP protein before coupling

A
  • inactive
  • trimeric
  • with alpha, beta and gamma subunits
46
Q

Describe adrenaline (epinephrine) action

A
  • triggers tissue-specific responses via cAMP
  • beta-adrenergic receptors are coupled to adenylate cyclase by G-proteins
47
Q

Describe adrenaline

A
  • 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
Q

cAMP

A

triggers glycogen breakdown via a kinase cascade

49
Q

Describe the glycogen breakdown kinase cascade

A
  • PKA dissociates from cAMP
  • phosphorylated by phosphorylase kinase (ATP -> ADP and Pi)
  • phosphorylated by glycogen kinase
  • glycogen converted to glucose 1-phosphate
50
Q

Describe feedback loops that desensitise beta-adrenergic receptors

A
  • GTP transferred from beta-adrenergic receptors to adenylate cyclase
  • reacts with ATP and cAMP to produce PKA
  • inactivated by phosphorylation
51
Q

List some hormone-induced cell responses mediated by cAMP

A
  • thyroid
  • adrenal cortex
  • ovary
  • muscle
  • bone
  • heart
  • liver
  • kidney
  • fat
52
Q

Describe the thyroid gland

A
  • TSH
  • thyroid hormone synthesis and secretion
53
Q

TSH

A

thyroid-stimulating hormone

54
Q

Adrenal cortex

A
  • ACTH
  • cortisol secretion
55
Q

ACTH

A

adrenocorticotrophic hormone

56
Q

Describe the ovary

A
  • LH
  • progesterone secretion
57
Q

LH

A

luteinising hormone

58
Q

Describe the muscle

A
  • adrenaline
  • glycogen breakdown
59
Q

Describe the bone

A
  • parathormone
  • bone resorption
60
Q

Heart

A
  • adrenaline
  • increase in heart rate and force of contraction
61
Q

Liver

A
  • glucagon
  • glycogen breakdown
62
Q

Kidney

A
  • vasopressin
  • water reabsorption
63
Q

Fat

A
  • adrenaline, ACTH, glucagon, TSH
  • triglyceride breakdown
64
Q

Describe the inositol signalling pathway

A
  • 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
Q

List some of the roles of the IP3/Ca2+ signalling pathway

A
  • metabolism
  • contraction
  • fluid secretion
  • neuronal synaptic plasticity
  • aggregation
  • ion channel opening
  • aldosterone secretion
  • differentiation
  • proliferation
  • exocytosis
66
Q

Describe the IP3/Ca2+ signalling pathway in metabolism

A

liver cells

67
Q

Describe the IP3/Ca2+ signalling pathway in contraction

A
  • ventricular cells
  • atrial cells
  • smooth muscle
  • mesangial cells
68
Q

Describe the IP3/Ca2+ signalling pathway in fluid secretion

A
  • intestinal cells
  • parietal cells
  • pancreas
  • salivary glands
  • sweat glands
69
Q

Describe the IP3/Ca2+ signalling pathway in neuronal synaptic plasticity

A
  • purkinje neurones
  • hippocampal neurones
70
Q

Describe the IP3/Ca2+ signalling pathway in aggregation

A

blood platelets

71
Q

Describe the IP3/Ca2+ signalling pathway in ion channel opening

A
  • astrocytes
  • T cells
72
Q

Describe the IP3/Ca2+ signalling pathway in aldosterone secretion

A

glomerulosa cell

73
Q

Describe the IP3/Ca2+ signalling pathway in differentiation

A
  • osteoblasts
  • brown fat cells
74
Q

Describe the IP3/Ca2+ signalling pathway in proliferation

A
  • T cells
  • mesangial cells
  • smooth muscles
  • brown fat cells
75
Q

Describe the IP3/Ca2+ signalling pathway in exocytosis

A
  • b-Cells
  • L Cells
  • mast cells
  • macrophages
  • parathyroid glands
  • astrocytes
  • renin-producing granular cells
76
Q

Describe the imaging of Ca2+-dynamics

A
  • in C. elegans pharyngeal muscle
  • using cameleon 2.1 (transgenic probes for Ca2+)
77
Q

Describe the role of phosphatidyl inositols as membrane scaffolds

A
  • PIP
  • PI(4)P
  • PI(4,5)P2
  • PI(3,4,5)P3
  • phosphorylation by PI 3-kinase
  • can interact with cytoskeleton
78
Q

What links PKA, CaM-kinase, PKC and MAPK

A

they are transcription regulators

79
Q

Summarise GCPR pathway 1

A
  • G protein
  • adenylyl cyclase
  • cyclic AMP
  • PKA
  • protein targeting/transcriptional regulation
80
Q

Summarise GCPR pathway 2

A
  • G protein
  • phospholipase C
  • IP3
  • Ca2+
  • calmodulin
  • CaM-kinase
  • protein targeting/transcriptional regulation
81
Q

Summarise GCPR pathway 3

A
  • G protein
  • phospholipase C
  • diacylglycerol
  • PKC
  • protein targeting/transcriptional regulation
82
Q

Summarise RTK pathway 1

A
  • phospholipase C
  • diacylglycerol
  • PKC
  • protein targeting/transcriptional regulation
83
Q

Summarise RTK pathway 2

A
  • Grb2
  • Ras-GEF (Sos)
  • Ras
  • MAPKKK
  • MAPKK
  • MAPK
  • protein targeting/transcriptional regulation
84
Q

Summarise RTK pathway 3

A
  • PI 3-kinase
  • PI(3,4,5)P3
  • (PDKT)
  • Akt kinase
  • protein targeting/transcriptional regulation
85
Q

Summarise RTK pathway 4

A
  • Grb2
  • Ras-GEF (Sos)
  • Ras
  • PI 3-kinase
  • PI(3,4,5)P3
  • (PDKT)
  • Akt kinase
  • protein targeting/transcriptional regulation
86
Q

Describe the analysis of downstream signalling in multiple MAPK pathways

A
  • 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
Q

Describe the cluster analysis of gene behaviour in yeast

A
  • > 200 gene transcripts found to increase in abundance
  • > 200 decrease in abundance
  • 383 genes changed by >3 fold
88
Q

Describe the testing of the pheromone hypothesis using mutants

A
  • 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
Q

ste2

A

pheromone receptor

90
Q

far1

A

cdk inhibitor

91
Q

Describe the acetylcholine receptor

A
  • 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
Q

Describe GABA and glycine receptors

A
  • 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
Q

GABA

A

gamma-amino butyric acid

94
Q

benzodiazepines

A

valium

95
Q

Describe ionotropic glutamate receptors

A
  • NMDA receptors
  • AMPA receptors
96
Q

Describe NMDA receptors

A
  • permeable to Ca2+
  • promote depolarisation
  • blocked by Mg2+ until ejected by depolarisation
97
Q

NMDA

A

N-methyl-D-aspartate

98
Q

Describe AMPA receptors

A
  • permeable to Na+
  • promote depolarisation
99
Q

AMPA

A

α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid

100
Q

Describe metabotropic glutamate receptors

A
  • glutamate receptors initiate a
    G-protein cascade that activates adenylate cyclase and PKA
  • Na+ channels activated by phosphorylation (by PKA)
101
Q

Summarise the G protein cascade

A
  • GDP to GTP
  • GTP binds adenylate cyclase
  • ATP to produce cAMP
  • releases pKA
  • goes to membrane receptor
102
Q

Describe 5-HT receptors activate channels directly, or via the IP3 and cAMP pathways

A
103
Q

5-HT

A
  • 5-hydroxytryptamine
  • serotonin

Trinity Term 1 (38 decks)

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