outline main stages of cell signalling
LSC
Ligand-receptor interaction
ligand r&b specific binding site of receptor on CSM/within target cell >
ligands complementary in shape to specific binding site of specific receptor protein
Signal transduction
ligand binding induces conformational change in receptor >
relay molecules, various proteins amplify & transduce signal into specific cellular response >
signals could be transmitted through 2nd messengers(cAMP)/phosphorylation cascades via protein kinases
Cellular response
transduced signal triggers specific cellular response, may be change in GE/catalysis by enzyme/rearrangement of cytoskeleton
describe molecular structure of GPLR & explain how its structure relates to its function
made up of 1 polypeptide w/ 7 transmembrane a-helices -> allows embedded in & span CSM >
has extracellular region(may be glycosylated) -> serve as specific binding site for ligand >
has intracellular/cytoplasmic region -> serve as specific binding site for G-protein
outline how insulin regulate blood glucose regulation
insulin r&b specific binding site on tyrosine kinase receptor(RTK) on liver/muscle CSM, causes 2 receptor polypeptides to undergo conformational change & dimerise >
dimerisation activates tyrosine kinase region of each polypeptide; each tyrosine kinase phosphorylates tyrosines of other polypeptide >
activated RTK recognised by specific relay proteins, pass signal on, leads to activation of glycogen synthase >
glycogen synthase catalyses glucose -> glycogen conversion(glycogenesis) >
any 1:
insulin also stimulates increase in rate of respiration using glucose as respiratory substrate, broken down & oxidised to CO2, H2O ;
increase in plasma membrane permeability of target cells to glucose, increase rate of uptake of glucose from blood by most body cells ;
glucose -> fats conversion for storage in adipose cells/tissues
outline how glucagon regulate blood glucose regulation
glucagon r&b specific binding site of GPLR on liver CSM, induces conformational change in receptor >
receptor binds to G protein, activates it; GTP molecule replaces GDP on G protein; activate G protein dissociates from receptor, activates adenyl cyclase >
adenyl cyclase catalyses conversion of ATP to cAMP >
cAMP acts as 2nd messenger, triggers downstream signalling events such that glycogen phosphorylase activated >
glycogen phosphorylase catalyses glycogen -> glucose breakdown(glycogenolysis) >
glucagon also stimulates increase in rate of conversion of amino acids, glycerol to glucose(gluconeogenesis) so that BGC increases, returns to normal
explain roles of kinases in signal amplification
enzyme; catalyses transfer of phosphate groups from phosphate-donating groups(ATP) to specific substrates -> phosphorylation >
phosphorylation activates protein >
active protein in turn activate other proteins, triggers numerous reactions in cell @ once
explain roles of phosphatases in signal amplification
enzyme; catalyses removal of phosphate groups from proteins by hydrolysis, reverses protein kinase action >
dephosphorylation deactivates protein
explain roles & nature of second messengers, cAMP
small, hydrophilic molecules; usually non protein >
second messengers(cAMP) relay signals received @ surface of cell by GPLR/RTK into cytoplasm/nucleus >
ligand r&b SBS on GPLR, receptor undergoes CC, binds & activates G protein >
G protein activates adenyl cyclase, catalyses conversion of ATP -> cAMP >
cAMP binds & activates another protein; activated protein triggers downstream signalling events(phosphorylation cascade), lead to cellular responses
describe phosphorylation cascade & signal amplification in signal transduction
phosphorylation cascade
activated protein kinase triggers downstream signalling events >
involves sequential phosphorylation of various other proteins/signal transmitted through phosphorylation cascade >
signal amplification
no. of protein molecules phosphorylated increases w/ each level of cascade >
relay molecules, various proteins amplify & transduce signal into specific cellular response
state similarities between GPLR and RTK
both have extracellular specific binding sites for ligands >
both change conf to trigger downstream signalling pathways/for signal transduction >
both have intracellular regions, interact w/ intracellular proteins >
both have extracellular & intracellular region
why must receptors, channel completely span CSM?
receptors need detect signals outside cell >
signals transduced/relayed to molecules inside cell >
receptors span CSM; polar/large ligands cannot pass thru hydrophobic core of transient pores of CSM, remain outside cell >
channels span CSM; transport polar molecules/charged ions, repelled by hydrophobic core of CSM >
channels enable polar molecules/charged ions move across membrane
outline advantages of cell signalling systems
polar/large ligand which cannot pass thru CSM r&b to receptor on CSM & activate specific protein within cell >
1 ligand molecule stimulate production of more than 1 second messenger, results in signal amplification >
provide diff points @ which cellular response can be regulated(activation of protein, conversion of molecules) >
allows ligand to trigger specific cellular responses due to collection of receptors, specific proteins & second messenger in target cells