cell signalling Flashcards
what are the three stages of cell signalling
- signal reception
- signal transduction
- cellular response
what is signal reception
it is when a signal molecule binds complementarily to a receptor protein, forming a ligand receptor complex which changes the conformation of the receptor protein
define signal transduction
it is the process where a cell converts a extracellular signal into an intracellular signal that results in a specific cellular response
what is the role of protein kinase
protein kinases transfers phosphate groups from ATP to a protein, phosphorylating it and hence activates protein kinase, turning on the signal transduction pathway
what is the role of protein phosphatases
protein phosphotases removes phosphate groups from proteins, dephosphorylating and thus deactivating protein kinase, turning off the signal transduction pathway. Hence, the protein kinase can be reused
what is the role of protein phosphatases
protein phosphotases removes phosphate groups from proteins, dephosphorylating and thus deactivating protein kinase, turning off the signal transduction pathway. Hence, the protein kinase can be reused
what are the roles and nature of second messengers
second messengers are small, non-protein, water soluble ions.
Binding of ligand to receptors stimulate an increase in concentration of second messengers which will diffuse across the cytosol to mount a large-scale, coordinated response
describe the 5 structures of G protein and link it to its function
1, hydrophobic AA residues form the inter-helical loops on N & C terminus, enabling extracellular and intracellular domains to be soluble in aqueous medium so as to interact with water soluble ligands and G protein
- hydrophobic AA residues in the 7 α helices and hydrophobic interactions between the α helices allow the membrane embedded domain to be stabilised and embedded within membrane bilayer
- the extracellular domain contains a specific AA at ligand binding site, enabling signal binding site to have a specific 3D conformation for interaction with specific ligand
- the intracellular domain contains specific AA at G protein interaction site, enabling G protein interaction site to have specific 3D conformation to bind and activate G protein
- Binding of a ligand to G protein linked receptor changes the conformation of protein, allowing it to interact with G protein, hence enabling GPLR to initiate signal transduction pathways via the activation of G protein
what are the steps of GPLR signalling
- ligand binds to extracellular site of GPLR and causes a conformational change in receptor, activating GPLR
- with an increased affinity for G protein, the cytoplasmic side of GPLR binds an inactive G protein, causing GTP to displace GDP bound to the G protein, activating the G protein
- activated G protein dissociates from the GPLR and diffuses along the membrane
- activated G protein binds to an enzyme, altering its activity
- change in enzyme activity initiate a cascade of signal transduction events, such as release of Ca2+ and production of cAMP
- the last activated molecule in the transduction pathway elicits a cellular response
how is the transduction pathway of G protein linked receptor inhibited
the intrinsic GTPase activity of G protein hydrolyses the bound GTP to GDP, inactivating G protein. LIgand will also dissociate from the GPLR. Hence, the inactive G proteins leaves the enzyme and is ready for reuse
how are Ca2+ ions released into the cytosol and what do they do
IP3 gated calcium channel in the endoplasmic reticulum opens and Ca2+ diffuses out of the ER down the concentration gradient, into the cytosol.
Ca2+ activate proteins in the signalling pathway
how are cytosolic Ca2+ levels kept low
x4
- calcium ATPase in ER keeps Ca2+ in the ER lumen
2, calcium ATPase actively pump Ca2+ from cytosol into the extracellular fluid - mitochondrial Ca2+ pumps Ca2+ into mitochondria
- sodium calcium exchangers couples the export of Ca2+ with facilitated diffusion of Na+ into the cytosol
outline the steps of glucagon-GPLR signalling
- glucagon binds to specific G protein linked receptor, activating G protein
- activated G protein activates enzyme adenylyl cyclase, synthesising large amounts of cAMP
- cAMP binds to and activates protein kinase A
- active protein kinase A phosphorylates and activates glycogen phosphorylase kinase while deactivating glycogen synthase by phosphorylating it. deactivation of glycogen synthase inhibits conversion of glucose to glycogen
- activated glycogen phosphorylase kinase phosphorylates glycogen phosphorylase, which breaks down glycogen into glucose
- glucose formed diffuses into bloodstream, increasing blood glucose concentration
what are the 2 features of receptor tyrosine kinase
- it has an intracellular tail containing multiple tyrosines and a tyrosine kinase domain
- receptor tyrosine kinases can trigger multiple signal transduction pathways, activating multiple cellular responses
outline the steps of insulin-RTK signalling
- binding of insulin to RTK activates the receptor’s tyrosine kinase, resulting in receptor aggregation and dimerisation
- dimerisation leads to activation of tyrosine kinase activity, resulting in auto-phosphorylation and receptor activation, where each tyrosine kinase domain adds a phosphate group from an ATP molecule to a tyrosine on the tail.
- relay protein that is specific to the insulin receptor binds to a specific phosphorylated tyrosine on the receptor and becomes activated
- activated relay proteins trigger a signal transduction pathway
- when downstream relay proteins are activated, there is movement of cytoplasmic vesicles carrying GLUT-4 glucose transporters, fusion of vesicles with plasma membrane and more glucose transporters for more glucose uptake.
- glycogen synthase is also activated, converting glucose to glycogen
