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Monash - BCH3042 > Area 2 Mechanisms of signalling > Flashcards

Area 2 Mechanisms of signalling Flashcards

Understanding what's required for cell signal transduction

1
Q

What are the 6 hallmarks of cancer?

A
  • Resisting cell death
  • Evading Growth suppressors
  • Sustaining proliferative signalling
  • Inducing angiogenesis
  • Enabling replicative immortality
  • Activating invasion and metastasis
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2
Q

What are the three main classes of hormones?

A
  1. Polypeptides (insulin)
  2. Peptide amine hormones (Epinephrine)
  3. Lipophilic hormones (estrogen/testosterone)
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3
Q

What two pathways can alter speed of downstream effects?

A

Fast - Altering protein function

Slow - Altering protein synthesis

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4
Q

What are the four forms of intercellular signalling?

Give examples of cells that do that signalling type.

A

Contact dependent - Immune cell killing
Paracrine - Immune cell cytokine signalling
Synaptic - Neurons and immune cell signalling
Endocrine - pancreatic cells to the muscles

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5
Q

How can signal strength and the amount of signals alter outcomes?

A

Signal strength can alter the commitment of cells to a lineage.

The amount of signals can alter how the cell reacts, each different signal altering the outcome slightly.

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6
Q

What are some examples of each of the types of hormones and their sources?

A

Polypeptide
Insulin - pancreas

Peptide amine
Epinephrine - adrenal gland (medulla)

Lipophilic
Steroid hormone - adrenal cortex

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7
Q

Can polypeptide hormones yield more than one hormone after translation?

A

Yes, through proteasomal cleavage a polypeptide can be broken down into many different hormones.

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8
Q

From which two amino acids are peptide amine hormones derived?

A

Tyrosine (thyroid hormone and adrenaline) or tryptophan (Melatonin)

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9
Q

From which molecule are the lipophilic hormones derived from?

A

Cholesterol

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10
Q

List qualities of hormone receptors.

A
  • Large proteins
  • Highly specific recognition sites
  • Location can be anywhere in/on cell
  • Amplify signals to result in biological action
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11
Q

There are hundreds of signals that impact every cell, how are a few selected as dominant?

A
  • Type of receptors
  • Number of intracellular messengers
  • Activity of downstream effectors
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12
Q

What are the four types of hormone receptors?

A

Ion channel coupled receptors
Nuclear receptors
G protein coupled receptors
Enzyme linked receptors

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13
Q

How to intracellular receptors change conformation to activate?

A

The ligand first must bind, following this the alpha helix of the coactivator protein must bind for full activation and transcription of target genes

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14
Q

How do G protein coupled receptors work?

A

The siganl moleucle binds to the receptor, this recruits the G protein coupled, the alpha subunit replaces GDP for GTP and separates from the beta and gamma units where both cause downstream signalling. This is halted by GTP hydrolysis to GDP.

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15
Q

How do enzyme linked receptors work

A

The binding of the signal molecule will cause homo or hetero dimerization and activation of a catalytic domain or recruitment of an enzyme

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16
Q

What is a molecular switch?

A

A molecule that can turn ‘on’ or ‘off’ to cause signalling. To turn on it receives incoming signals and then transmits these signals, negative feedback turns it ‘off’

17
Q

What are the 6 main members of the enzyme linked receptors?

A
  1. Receptor tyrosine kinases (phosphorylated tyrosine)
  2. Tyrosine kinase associated receptors (couple to proteins and have tyr kinase activity)
  3. Receptor Serine/Threonine kinases (phosphorylate Ser or Thr)
  4. Histidine-kinase associated receptors
  5. Receptor tyrosine phosphatases (remove Tyr phospho)
  6. Receptor guanylyl cyclases (catalyse the production of cGMP)
18
Q

What are the two types of molecular switches?

A

signal by phosphorylation

signal by GTP binding

19
Q

What is the components of the G coupled receptors

A

a 7 transmembrane surface receptor, a trimeric G protein (alpha, beta and gamma subunits) with a GTP/GDP binding site

20
Q

For the GTP binding molecular switches, where do GAP and GEF fall in?

A

GEF -Guanine nucleotide exchange factors
GAP - GTPase activating proteins
GAPs dephosphorylated GTP on the switch (more rapid turn off)
GEFs swap GDP for GTP on the switch

21
Q

Which G protein subunit is best known to cause downstream signalling?

A

The Alpha subunit

This is involved in smell, taste, and light perception

22
Q

How many different types of G protein coupled receptor subunits have been found in humans

A

A - 20
B - 6
Y - 11

23
Q

Give examples of G protein secondary messengers and the tertiary messengers

A

Adenylate cyclase -> Cyclic AMP
Phospholipase C -> Diacylglycerol (DAG) and Inositol 1,4,5-triphosphate (IP3)
Phospholipase A2 -> Arachidonic acid

24
Q

How does cyclic AMP activate PKA? What happens downstream of PKA?

A

cyclic AMP binds the allosteric inhibitor of PKA releasing the active form. PKA translocates to the nucleus where it phosphorylates CREB leading to altered gene expression.

25
Q

What is a zinc finger?

A

A finger like loop of peptides enclosing a bound zinc ion at one end typically part of a larger molecule (usually one involving transcription)
Each zinc finger has its own role, they can be used tof DNA binding.

26
Q

Which types of nuclear receptors are likely to:
1 - activated gene expression?
2 - activated gene repression?

A

1 - Ligand activated receptors

2 - apo nuclear receptor (no ligand

27
Q

What disease is associated with excess cortisol?

A

Cushing’s Syndrome

28
Q

Whihc molecular drug is used to treat cushings and by what mechanism?

A

RU486/Mifepristone

Glucocorticoid Receptor /Progesterone Receptor antagonist

29
Q

What is involved in congenital adrenal hyperplasia?

A

A range of diseases caused by mutations in genes for enzymes involving cortisol conversion to later steroid hormones

30
Q

What is the mechanism of action for a nuclear receptor?

A
  • Ligand binds to receptor
  • Cytosolic complex and inhibitory proteins dissociate
  • Conformation change allowing coactivator binding
  • DNA binding increasing level of RNA pol II transcription
31
Q

What are the type 1 and type 2 nuclear receptors?

A

type 1
steroid hormone receptors (form homodimers to make binding site)
type 2
RXR-NRs binding as heterodimers

32
Q

What are some Coactivators and corepressors?

A

Coactivators
1 - Chromatin remodeling
2 - Histone acetyltransferase (HATs)
3 - Activators

Corepressors
Histone deacetyltransferases (HDACs)

Monash - BCH3042 (7 decks)

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