cell signalling Flashcards
describe the link between enzymes and phosphorylation
> some enzymes are deactivated by phosphorylation ( protein kinase - add a phosphate)
activated by dephosphorylation (protein phosphatase - take away a phosphate)
What are the different types of cell to cell signalling?
1) tight junctions
2) adherens junctions
3) desmosomes
4) gap junctions
describe the broad steps that occur in a cell surface receptor
1) recognition
- extracellular signal molecule (ligand) binds to receptor protein
2) transduction
- signal is transduced or integrated, causes a conformational change inside the cell
- creates a second messenger
3) transmission
- the message is transmitted from the second messenger to the effector (could be enzymes, ion channels and transcription factors)
4) modulation
- of effector
- activation of protein kinases or phosphatases
5) response
- leads to a response in the cell can be an integration of multiple signals at once
6) termination
What are the different types of cell receptors?
1) ligand-gated ion channels
2) catalytic receptors
3) nuclear receptors
4) nuclear receptors
4) G-protein-coupled receptors
Describe gated ion channels
- integral membrane proteins with a gate
- respond to different signals in cell:
> changes in membrane potential
> second messengers - signals from inside the cell
> ligands that bind to a receptor on the outside of the cell
describe ligand-gated ion channels
> multi subunit transmembrane proteins
opening/closing of the channel (thus ion transport) is controlled by binding to a site on the receptor = ‘ionotropic receptors’
the ligand itself actually controls the opening and closing of the gate by binding to the receptor
describe catalytic receptors
> also known as enzyme linked receptors
are either enzymes themselves or part of an enzyme complex
important ATM is receptor protein tyrosine kinases (RTKs)
RTKs often activated by growth factors and metabolic regulators (insulin binds to this type of receptor)
they often promote cell differentiation and maturation -> wound healing
they require receptor dimerisation, which means that activation is both receptor and ligand mediated.
dimerisation causes transautophosphorylation, where intracellular portion of one receptor dimer phosphorylate the other
signalling proteins recognise and bind to these phosphorylated areas on the intracellular surface of the protein receptor
describe nuclear receptors
> some ligands bind directly to and activate nuclear receptors
often steroids, pKA
these receptors have the ability to directly bind with DNA and regulate the expression of and regulate the expression of adjacent genes = transcription factors
describe the role of nuclear receptors in wound healing
> immune cells secrete ligands
bind to fibroblast nuclear receptor
binding to DNA receptor - initiate gene expression
more collagen is made -> granulation tissue to heal wound
describe G=protein coupled receptors
> ligands = hormones, neurotransmitters, chemokines, nucleotides, light, ordants (smell), and tastants
same ligand can activate different GPCRs on different cell types
- epinephrine can activate 9 dif GPCR
- Acetylcholine can activate 5 different GPCRs
largest family of integral membrane proteins on cell surface
receptor is bound to g proteins
made up of 7 transmembrane domains
- EC portion is the amino terminus and the IC is the carboxyl termini
the ligand binding causes a conformational change which induces release of GDP attached to alpha subunit, and simultaneous binding of GTP instead. This activate the complex, and this GTP alpha subunit can deattach from the complex and activate other processes in the cell. when GDP binds to the Alpha subunit, it deactivates the cascade.
What are some affects of toxins on GPCRs?
> cholera toxin modifies G proteins
- Galpha subunit remains in the ATP active form
- increased ion conductance and water flow
= diarrhoea
e.coli and salmonella have similar affects
bordetella pertussis causes the inhibition of the alpha subunit.
What is cAMP and describe its role in GPCRs
1) ligand -receptor binding activates a G protein
2) G protein activates adenylate cyclase ( membrane bound enzyme)
3) adenylate cyclase produces cAMP from ATP
4) cAMP activates protein kinases
5) protein kinases phosphorylate enzymes, this activates some and deactivates others
6) activated enzymes catalyse metabolic reactions with a wide range of possible effects on the cell
- the activity of ion channels by phosphorylation = fast response
- Pka can move into the nucleus of the cell and regulate transcription factors -> induction or repression of gene expression -> slow response
What is the role of GPCRs in wound healing?
Epithelialisation
> GPCR activated by a hormone or growth factor
> 2nd messenger cAMP activates signalling proteins that activate proteases
> those break down the proteins that hold epithelial cells together
> these cells migrate and differentiate to repair site of wound
re-modelling
> GPCRs activate release of calcium stores which may activate proteases
> can also activate gene expression via other protein kinases
