cell signalling Flashcards
why are receptor proteins located at the cell surface membrane?
receptor proteins are water-soluble and too large to cross the hydrophobic core of the phospholipid bilayer in the cell surface membrane
how does the ligand bind to the receptor protein
shape of the ligand is complementary to the shape of the receptor protein
define phosphorylation cascade
a sequence of signalling pathway events where one kinase phosphorylates another kinase, causing a chain reaction leading to the phosphorylation of thousands of proteins
explain the process of dephosphorylation
after the cellular response is carried out, protein phosphatases (enzyme) remove phosphate groups from the protein kinases, returning them back to their inactive state
why is a very low concentration of signal molecules sufficient to result in a much greater cellular response?
each activated relay molecule can activate many more molecules in the next step, thereby resulting in a much greater number of activated products than in the preceding step
what are second messengers?
small non-protein molecules/ions, water-soluble and readily spread through out the cell by diffusion
how is cellular response brought about?
the relay molecules pass the information of the signal to the last step of the signal transduction pathway where the effector protein is activated
name some cellular responses which can take place (three)
changes in level of enzyme activity, regulation of gene expression, rearrangement of cytoskeleton for various functions
how does signal termination occur? (three)
- dissociation of ligand from receptor
- degradation of ligand, second messenger or other relay molecules
- desensitisation of receptors
examples of degradation of ligand,second messenger or other relay molecules for signal termination (three)
- GTPase in G protein hydrolyses bound GTP into GDP
- phosphodiesterase converts cAMP into AMP
- dephosphorylation of protein kinases by protein phosphatases
where are signal molecules obtained from?
signal molecules are produced by signalling cells which incorporate them into molecules before releasing them into the extracellular space via exocytosis, where they can be transported to the target cell
how is one signal molecule able to elicit different cellular responses from the same cell?
one signal molecule can activate more than one signal transduction pathway due to the branching of the pathway
how is one type signal molecule able to elicit different cellular responses from different cells?
one type of signal molecule can bind to receptor proteins of different cells as long as the shape is complementary, producing different cellular responses
how can a cellular response be controlled?
strength of cellular response is controlled by interactions between signalling pathways via protein “cross-talk”
what does GPCR stand for?
G protein-coupled receptor
describe the structure of GPCR
it is made up of a single polypeptide chain which is folded into 7 a-helices embedded in the transmembrane region of the cell surface membrane
=>an extracellular ligand-binding site and an intracellular G protein binding site
when is G protein in its active and inactive conformation?
active when bound to GTP
inactive when bound to GDP
outline the mechanism of action of GPCR
- GPCR and G protein are inactive (G protein bound to GDP)
- binding of ligand to the extracellular side of GPCR causes a conformational change activating it
- activated GPCR binds to inactive G protein
- GTP displaces the GDP bound to G protein, activating it
- the activated G protein then dissociates from GPCR and moves along the cell surface membrane until it reaches adenylyl cyclase, changing its conformation and activating it
- activated adenylyl cyclase triggers a signal transduction pathway leading to a cellular response
- the GTPase enzyme in the G protein then rapidly hydrolyses GTP into GDP causing the G protein to return to its inactive form
- inactive G protein dissociates from adenylyl cyclase which becomes inactive
- thus, signal is terminated
what does RTK stand for?
receptor tyrosine kinase
describe the structure of RTK
made of 2 polypeptide chains
=> each polypeptide subunit has 1 a-helix embedded in the transmembrane region
=>extracellular ligand binding site and intracellular tail with multiple tyrosine residues
=>inactive when 2 polypeptide subunits are separate
=> active when 2 polypeptide subunits are linked as a dimer
outline the mechanism of action of RTK
- RTK is in its inactive form and exists as 2 separate subunits
- binding of ligand to the extracellular side of RTK causes the 2 subunits to associate closely with each other to form a dimer in a process called dimerisation
- dimerization activates the tyrosine kinase region of each subunit
- the tyrosine kinase region of each subunit can now phosphorylate the tyrosine residues on the intracellular tail of the other subunit via cross-phosphorylation
- both subunits are now phosphorylated and receptor is fully activated
- relay proteins in the cell can now bind to phosphorylated tyrosine residues on the receptor
- the bound proteins then undergo a conformational change and becomes activated
- each activated relay protein then triggers a signal transduction pathway, eventually leading to a cellular response
- one RTK dimer may activate many intracellular relay proteins, triggering different signal transduction pathways and cellular responses simultaneously
- after specific cellular responses have taken place, the signal is terminated by phosphatases
what is the level of blood glucose at which insulin is secreted?
when blood glucose levels increase above 90mg per 100 ml of blood
how is insulin secreted to trigger a cellular response?
increase in blood glucose levels beyond 90mg per 100ml of blood is detected by islets of Langerhans resulting in the secretion of insulin by the B-cells of islets of Langerhans via exocytosis into the bloodstream for transport to the target cells (liver and muscle cells)
=> it then triggers the uptake of glucose from blood to decrease blood glucose levels
outline the action of insulin to trigger a cellular response
- At the target cells, insulin binds to the extracellular side of the insulin RTK receptor resulting in a conformational change, activating the receptor tyrosine kinase (RTK)
- the tyrosine kinase of each subunit can now phosphorylate the tyrosine residues on the intracellular tail of the other subunit via cross-phosphorylation
- both subunits are now phosphorylated
- the receptor is fully activated
- different intracellular relay proteins will bind to specific phosphorylated tyrosine residues on receptor subunits
- the tyrosine kinase of the receptor phosphorylates these relay proteins
=>phosphorylation cascade is triggered
=>more than one signal transduction pathway can be activated due to the activation of different relay proteins - the activation of the effector protein of the signal transduction pathway results in a cellular response
- one cellular response is an increase in the amount of glucose transporters (GLUT4) on the cell surface membrane
- this increases the permeability of the cell membrane to glucose. increasing uptake of glucose into the cells from the blood
- signal termination
what are other cellular responses which may arise from action of insulin?
increased rate of glycogenesis (conversion of glucose to glycogen)
increased rate of protein synthesis
increased rate of lipogenesis
decreased rate of gluconeogenesis (conversion of other non-carbohydrate carbon substrates to glucose
what is the level of blood glucose at which glucagon is secreted?
when blood glucose levels decrease below 90mg per 100 ml of blood
how is glucagon secreted to trigger a cellular response?
decrease in blood glucose levels below 90 mg per 100 ml of blood is detected by islets of Langerhans triggering the secretion of glucagon by a-cells of islets of Langerhans via exocytosis into the bloodstream for its transport to the target cells (liver cells)
=> it then triggers the release of glucose from the target cells into the blood to increase blood glucose levels
outline the action of glucagon to trigger a cellular response
- At target cells, glucagon binds to the extracellular side of the glucagon GPCR receptor inducing a conformational change, activating it
- the intracellular side of GPCR binds to inactive G protein
- this causes a GTP molecule to displace the GDP molecule bound on G protein activating it.
- activated G protein then dissociates from the GPCR and moves along the cell surface membrane until it reaches an adenylyl cyclase, changing its conformation and activating it
- the activated adenylyl cyclase catalyses the conversion of ATP into cyclic AMP
- cAMP acts a second messenger and activates protein kinase (protein kinase A)
- activated protein kinase then activates another protein kinase in a phosphorylation cascade
- this eventually results in the activation of effector protein (glycogen phosphorylase A)
- activated effector protein catalyses the breakdown of glycogen to glucose
- this increases the release of glucose into the bloodstream and restores the normal level of blood glucose
- signal termination
what is another cellular response which may arise from action of glucagon?
inactivation of an enzyme (glycogen synthase) that reduces the rate of glycogenesis (conversion of glucose into glycogen for storage)
