Cell signalling Flashcards
what is signal transduction
a way in which cells gain information about the environment
the coversions of signals into cellular responces
outline the process of signal transduction
1) a ligand binds to a specific binding pocket on the extracellular membrane of the receptor
2) binding causes a conformational of the receptor activating messengers
3) these messengers induce a specific cellular responce
why is signal transduction relevant
1) mediates direct cell to cell communication
2) coordinates metabolic processes within cells, the growth and differenciatino of tissues and the synthesis of proteins
3) coordinates the aggregation of free living cells for sexual mating
what causes receptor activation
1) binding of molecules
2) changes in conc of a metabolite
3) physical stimuli
what are the different types of signalling
1) endocrine
2) paracrine
3) autocrine
what is endocrine signalling
when signalling molecules are released by a cell and affect target cells distant from site of synthesis
e.g. hormones
what is paracrine signalling
the signalling molecules released by a cell affect target cells only in close proximity
e.g. growth factors or conduction by a neurotransmitter from one nerve cell to the next
what is autocrine signalling
when cells respond to substances that they themselves have released
e.g.
tumour cells produce growth factors which stimulate proliferation of themselves
what is intracellular signal transduction
pathways inside the cell which transduce signals downstream from the cell surface activation
outline the process of intracellular signal transduction
1) binding of ligands to cell surface receptors leads to a change in conc of low molecular weight intracellular signalling molecules (SECNDARY MESSENGERS)
2) the altered conc leads to activation of intracellular proteins within the signal transduction pathway
give some examples of secondary messengers
1) cycloic nucleotides e.g. cAMP
2) lipid messengers e.g. DAG
3) ions such as CA2+
outline the adenyl cyclase pathway
1) epinephrine binds to a G-coupled receptor
2) G protein activates adenyl cyclase
3) adenyl cyclase releases cAMP (secondary messenger)
4) cAMP activates kinase A protein which activates the enyme within the pathway
5) enzyme produces the desired product
what proteins are used to help transduce signals downstream from activated cell surface
1) G-proteins
2) kinases
3)phosphatases
what are G proteins
guanine nucleotide-binding proteins
- interact with other proteins to change and perpetuate the signal and is in a state of ‘on of off’
what are protein kinases
enzymes which catalyse the addition of phosphates to a substarte protein
what are phosphatases
enzymes which catalyse the removal of a phosphate from a substrate proteins
when is a G protein considered on and off
on- GTP bound
off - GDP bound
what happens when a G protein is on
1) two protein domains are bound to the terminal phosphate of GTP allowing the protein to bind and activate other signalling proteins
what happens when a G protein is off
release of the phosphate by GTPase catalysed hydrolysis causes domain I and II to releax into GDP
what are the two protein kinases found in animal cells
1) add phosphate group to the hydroxyl group tyrosine residues
2) add phosphate gro0up to the hydroxyl group of serine and threnonine residues
outline the structure of G protein-coupled receptors
1) several membrane spanning regions
2) N-terminal segment o the exoplasmic face outside the cell
3) C-terminal segment on the cytosolic face inside the cell of the plasma membrane
where can G protein coupled receptors be found
1) light activated receptors in the eye
2) odarant receptors in the mammalian nose
3) receptors for a number of hormones and neurotransmitters
outline how G proteins are associated with ligand induced activation of effector proteins
1) trimeric G proteins are tethered to the membrane by covalent attached lipid molecules
2) ligand binds to the receptor
3) receptor binds to G protein causing a conformational change in the alpha subunit
4) GDP dissociates with GTP activates G protein causing another change
5) this activates alpha subunit and beta-gamma complex and alpha dissociates
6) now can regulate activity of target proteins relaying signal
7) alpha hydrolysis GTP to GDP which reforms inactive g protein with beta-gamma complex
what is meant by ligand induced activation associated with G proteins
many G proteins coupled receptors have an extracellular ligand domain and when a protein ligand binds to this domain the receptor undergoes a conformational change which activates a trimeric GDP protein
what is the structure of trimeric G protein
composed of three protein subunits called alpha beta and gamma
the alpha and beta have covalently attached lipid tails which anchor protein to membrane
how can G proteins activate ion channels
binding of acetylcholine triggerd activation of G protein
the release of G-beta subunit binds to and opens associated effector, the K+ channel
give an example of light activated G-coupled receptors
the human retina has two photoreceptors rods and cones
what are the rods and cones of the eye involved in
cones = colour vision = G proteim coupled receptor is iodopsin
rods= stimulated by weak light GPTC= rhodospsin
