Area 2 Mechanisms of signalling Flashcards
Understanding what's required for cell signal transduction
What are the 6 hallmarks of cancer?
- Resisting cell death
- Evading Growth suppressors
- Sustaining proliferative signalling
- Inducing angiogenesis
- Enabling replicative immortality
- Activating invasion and metastasis
What are the three main classes of hormones?
- Polypeptides (insulin)
- Peptide amine hormones (Epinephrine)
- Lipophilic hormones (estrogen/testosterone)
What two pathways can alter speed of downstream effects?
Fast - Altering protein function
Slow - Altering protein synthesis
What are the four forms of intercellular signalling?
Give examples of cells that do that signalling type.
Contact dependent - Immune cell killing
Paracrine - Immune cell cytokine signalling
Synaptic - Neurons and immune cell signalling
Endocrine - pancreatic cells to the muscles
How can signal strength and the amount of signals alter outcomes?
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.
What are some examples of each of the types of hormones and their sources?
Polypeptide
Insulin - pancreas
Peptide amine
Epinephrine - adrenal gland (medulla)
Lipophilic
Steroid hormone - adrenal cortex
Can polypeptide hormones yield more than one hormone after translation?
Yes, through proteasomal cleavage a polypeptide can be broken down into many different hormones.
From which two amino acids are peptide amine hormones derived?
Tyrosine (thyroid hormone and adrenaline) or tryptophan (Melatonin)
From which molecule are the lipophilic hormones derived from?
Cholesterol
List qualities of hormone receptors.
- Large proteins
- Highly specific recognition sites
- Location can be anywhere in/on cell
- Amplify signals to result in biological action
There are hundreds of signals that impact every cell, how are a few selected as dominant?
- Type of receptors
- Number of intracellular messengers
- Activity of downstream effectors
What are the four types of hormone receptors?
Ion channel coupled receptors
Nuclear receptors
G protein coupled receptors
Enzyme linked receptors
How to intracellular receptors change conformation to activate?
The ligand first must bind, following this the alpha helix of the coactivator protein must bind for full activation and transcription of target genes
How do G protein coupled receptors work?
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.
How do enzyme linked receptors work
The binding of the signal molecule will cause homo or hetero dimerization and activation of a catalytic domain or recruitment of an enzyme
What is a molecular switch?
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’
What are the 6 main members of the enzyme linked receptors?
- Receptor tyrosine kinases (phosphorylated tyrosine)
- Tyrosine kinase associated receptors (couple to proteins and have tyr kinase activity)
- Receptor Serine/Threonine kinases (phosphorylate Ser or Thr)
- Histidine-kinase associated receptors
- Receptor tyrosine phosphatases (remove Tyr phospho)
- Receptor guanylyl cyclases (catalyse the production of cGMP)
What are the two types of molecular switches?
signal by phosphorylation
signal by GTP binding
What is the components of the G coupled receptors
a 7 transmembrane surface receptor, a trimeric G protein (alpha, beta and gamma subunits) with a GTP/GDP binding site
For the GTP binding molecular switches, where do GAP and GEF fall in?
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
Which G protein subunit is best known to cause downstream signalling?
The Alpha subunit
This is involved in smell, taste, and light perception
How many different types of G protein coupled receptor subunits have been found in humans
A - 20
B - 6
Y - 11
Give examples of G protein secondary messengers and the tertiary messengers
Adenylate cyclase -> Cyclic AMP
Phospholipase C -> Diacylglycerol (DAG) and Inositol 1,4,5-triphosphate (IP3)
Phospholipase A2 -> Arachidonic acid
How does cyclic AMP activate PKA? What happens downstream of PKA?
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.
