3.1: cell signalling

Question 1

what is a ligand

Answer 1

molecules produced by signalling cells that interact w receptors

1. large, hydrophilic, polar charged -> repelled by hydrophobic core of PL
2. small, hydrophobic, non-polar, uncharged -> diffuse across plasma membrane into cytoplasm

Question 2

what is a second messenger

Answer 2

small, non-protein, water-soluble molecules

Question 3

why are second messengers small and water soluble

Answer 3

rapid diffusion thru cell

quick transduction of signal

Question 4

why are second messengers non-protein and small

Answer 4

• less sensitive to pH/temp
• less easily degraded
• synthesised in shorter time
• less resources needed than larger molecules

Question 5

function of second messengers

Answer 5

1. relay signals from ligand binding (1st messenger) at cell surface receptors to target molecules in cytosol/nucleus
2. greatly amplify strength of signal -> large cellular response

Question 6

cell signalling: ligand-receptor interaction

Answer 6

1. recognition and reversible binding of ligand to specific receptor (complementary 3D conformation)
2. activation of receptor
3. ligand-receptor complex

Question 7

cell signalling: signal transduction

Answer 7

1. conformational change to specific receptor
2. signal converted and amplified via second messengers & phosphorylation cascade of kinases

Question 8

cell signalling: cellular response

Answer 8

activation of specific cellular activity

1. regulation of protein/enzyme activity
2. regulation of protein synthesis via gene expression
3. apoptosis

etc

Question 9

homeostasis

Answer 9

allow metabolic rxns to occur at optimum rate

• self regulation
• negative feedback

Question 10

advantages of cell signalling system

Answer 10

1. specificity of ligand-receptor int = specific response from specific target cells
2. activation of gene expression in nucleus
3. activate many target cells simultaneously = regulation and control of response
4. signal amplification = one signal molecule -> large cellular response
5. one signal molecule -> activate multiple pathways = rxns simultaneously

Question 11

kinase as a molecular switch

Answer 11

• ADDS phosphate grps
• activates proteins
• involved in signal amplification

Question 12

phosphotase as a molecular switch

Answer 12

• REMOVES phosphate grps
• deactivates proteins
• signal termination

Question 13

generally, how can a signal be terminated?

Answer 13

1. dissociation of ligand from receptor
2. GTPase hydrolyses bound GTP to GDP
3. phosphodiesterase converts cAMP to AMP
4. protein phosphotases inactivate kinases via dephosphorylation

Question 14

RTK: L-R interaction

Answer 14

1. insulin binds to extracellular binding sites of RTK
2. activates RTK protein
3. dimerises 2 RTK proteins
4. intracellular domain of RTK undergoes conformational change
5. intrinsic tyrosine kinase is activated
6. tyrosine kinase adds phosphate grp from ATP to tyrosine residues on tail of other RTK via autophosphorylation

Question 15

RTK: signal transduction

Answer 15

1. activated RTK triggers assembly of relay proteins
2. relay proteins further recruit and activate other downstream relay molecules and kinases
3. at each step, each activated kinase phosphorylates and activates a large no of next kinase
   SIGNAL AMP

Question 16

RTK: cellular response

Answer 16

1. glycogen synthase activated = GLYCOGENESIS ( glucose -> glycogen)
2. vesicles embedded w glucose transporters fuse w plasma membrane = increase glucose uptake
3. decrease in glycogenolysis and gluconeogenesis
4. decrease in blood glucose level back to set pt = NEGATIVE FEEDBACK

Question 17

RTK: signal termination

Answer 17

1. insulin dissociates from RTK = inactivation of RTK
2. phosphotase dephosphorylates tyrosine residues on RTK tails -> dimer dissociates back into individual RTK proteins
3. phosphotases inactivate protein kinases by dephosphorylation

Question 18

GPLR: L-R interaction

Answer 18

1. glucagon binds to extracellular site of GPLR
2. causes conformational change in GPLR
3. cytoplasmic side of activated GPLR binds inactive G protein
4. G protein exchanges bound GDP for GTP
5. activation and dissociation of G protein
6. dissociated active G protein binds and activated adenlyl cyclase

Question 19

GPLR: signal transduction

Answer 19

1. adenlyl cyclase catalyses conversion of ATP -> cAMP
2. second messenger cAMP binds and activates a large no of PKA (protein kinase A)
3. each activated kinase will initiate sequential phosphorylation -> phosphorylation cascade
4. at each step of the cascade, each kinase can activate a large no of kinases -> signal amplification
5. activated PKA P+A phosphorylase kinase -> glycogen phosphorylase

Question 20

GPLR: cellular response

Answer 20

1. large no of glycogen phosphorylase activated = glycogenolysis (glycogen -> glucose)
2. increase in gluconeogenesis
3. decrease in glycogenesis and glycolysis
4. increase in blood sugar conc to set pt = NEGATIVE FEEDBACK

Question 21

GPLR: cellular response

Answer 21

1. large no of glycogen phosphorylase activated = glycogenolysis (glycogen -> glucose)
2. increase in gluconeogenesis
3. decrease in glycogenesis and glycolysis
4. increase in blood sugar conc to set pt = NEGATIVE FEEDBACK

Question 22

GPLR: signal termination

Answer 22

1. glucagon dissociates from GPLR
2. GTPase intrinsic to G protein hydrolyses bound GTP -> GDP
3. phosphodiesterase converts cAMP -> AMP
4. phosphotases inactivate protein kinases via dephosphorylation