Cell Signalling

Question 1

What are the stages of cell signalling ?

Answer 1

1. Ligand-receptor interaction
   2, signal transduction
2. Cellular response

Question 2

Describe ligand-receptor interaction

Answer 2

Specific ligand binds to specific ligand binding site on the receptor protein, causing conformational change and activating the receptor.

Question 3

What are the types of receptors ?

Answer 3

1. Tyrosine kinase receptor
2. G-protein linked receptor
3. Ion channel receptor

Question 4

Where are these receptors found ?
What does this imply about their nature ?

Answer 4

Embedded at the cell surface membrane

Transmembrane domain: have hydrophobic R groups allowing them to embed in hydrophobic core of phosplipid bilayer

Intra/Extracellular domain: have hydrophilic R groups allowing them to intereact with aqueous surroundings

Question 6

What happens after receptor is activated from ligand-receptor interaction ?

Answer 6

Intracellular domain is able to intersect with an activated other proteins for signal transduction

IN RTK:
Activated intracellular kinase domain cross-phosphorylate tyrosine residues on cytoplasmic tails of receptors

Question 7

What is dimerisation ?

Answer 7

When receptor is split into 2 but close together when ligand binds

Question 8

Describe signal transduction and how it’s done ?

Answer 8

Multi step pathway, at each step, signal transduced into different form through conformational change of protein, activating the protein

Done by
1. Phosphorylation
2. Second messengers

Question 9

Describe phosphorylation and dephosphorylation of proteins in signal transduction

Answer 9

Phosphorylated by kinase
Dephosphorylated by phosphatase

Protein kinase added phosphate group from ATP to inactive protein, causing conformational change, activating the protein.
(Generating ADP)

Question 10

Describe the role of second messengers in signal transduction

Answer 10

Second messengers are small and after soluble abd can spread throughout the cell via diffusion.
They bind to relay proteins, causing conformational change to activate them

Question 11

Explain cAMP as a second messanger

Question 12

What are the types of cellular response ?

Answer 12

1. Cytoplasmic response
2. Nuclear response

Question 13

Describe cytoplasmic response

Answer 13

Change in activity of enzymes and proteins in cytoplasm
E.g: inhibition, synthesis

Question 14

Describe nuclear response

Answer 14

Specific gene coding for the synthesis of certain enzymes or proteins switched on or off

Question 15

What allows signal amplification ?

Answer 15

1. Phosphorylation cascade
2. Second messengers

Question 16

How does phosphorylation cascade lead to signal amplification ?

Answer 16

Each activated relay protein can activate multiple molecules of a downstream relay protein

Question 17

How does second messengers lead to signal amplification ?

Answer 17

Each active enzyme catalyses the formation of many second messnagers.
Each second messengers can bind to and activate a specific protein

Question 18

What type of receptor is insulin ?

Answer 18

Tyrosine kinase receptor

Question 19

What cells detect how increase in blood glucose ? And what do they secrete ?

Answer 19

B cells of the islet of langerhans in pancreas
Secrete insulin

Question 20

Why are insulin and glucagon receptors found on cell surface membrane and not in the cell

Answer 20

Insulin and glucagon are globular protein with hydrophilic R groups pointed towards the exterior cannot pass through hydrophobic core of csm

Question 21

What is the target cells of insulin ?

Answer 21

Liver and muscle cells

Question 22

Outline the ligand-receptor interaction stage of Insulin

Answer 22

Before binding, Insulin receptor is an inactive covalent disulfide-linked dimer, consisting 2 polypeptides.

Insulin binds to the specifically to ligand binding sit on insulin receptor, causing conformational change.

Tyrosine kinase region of of each polypeptide activated and in contact with the tyrosine residues in the cytoplasmic region of the other subunit, allowing cross-phosphorylation of tyrosine residues

Question 23

Describe the signal transduction pathway of insulin ?

Answer 23

Relay proteins recognise and binds to phosphorylated tyrosine residues on activated insulin receptor, causing conformational change in relay proteins, activating it.

Activated relay proteins leave receptor and bind to other downstream proteins to activate them.

This triggers phosphorylation cascade as each activate relay protein can activate multiple molecules of a downstream protein. (Signal amplification）

Question 24

Describe cellular response of insulin pathway

Answer 24

1. Vesicles in the cytoplasm that contain glucose carriers move and fuse to cell surface membrane, increasing rate of glucose uptake via facilitated diffusion.
2. Glucokinase is activated, phosphorylated glucose into glucose-6-phosphate for glycolysis
3. Stimulates glycogenesis (glycogen synthase activated) , ihhibits glycogenolysis (glycogen phosphorylase inhibited) , inhibits gluconeogenesis

Question 25

What is 1. Glycolysis 2. Glycogenesis 3. Glycogenolysis 4. Gkuconeogenesis

Answer 25

1. Break down of glucose 2. Synthesis of glycogen 3. Breakdown of glycogen 4. Synthesis of glucose

Question 26

What type of receptor glucagon receptor ?

Answer 26

G-protein linked receptor

Question 27

What cells detect how decrease in blood glucose ? And what do they secrete ?

Answer 27

a cells in islet of langerhans in pancreas Secrete glucagon

Question 28

What are the target cells of glucagon ?

Answer 28

Liver cells

Question 29

Outline ligand-receptor interaction stage of glucagon

Answer 29

Inactive glucagon receptor bonded to G-protein which carries a GDP molecule Glucagon binds specifically to ligand binding site of glucagon receptor, causing conformational change change, activating it. Activated receptor causes activation of G-protein as GTP displaces GDP.

Question 30

Describe the structure of glucagon

Answer 30

Extracellular domain: a helices forming ligand binding site Tranmembrane domain: 7 a helices with hydrophobic R groups projecting upwards to hydrophobic core of phospholipid bilayer of membrane Intracellular domain: Binding site complemtary to shape of G-protein

Question 31

Outline signal transduction pathway of glucagon

Answer 31

Activated G protein dissociates form receptor and binds to and activates adenylyl cyclase. Activated adenylyl cyclase catalyses conversion of ATP into cAMP. CAMP serves as second messengers bind to and activates protein kinase A. Activated protein kinase A catalyses activation of phosphorylation kinase. Activated phosphorylase kinase catalyses activation of glycogen phosphorylase.

Question 32

Is there amplification in phosphorylation of PKA ?

Answer 32

No. Since there’s only activation of 1 kinase (phosphorylase kinase)

Question 33

Why are changes in adenylyl cyclase and G-protein only temporary ?

Answer 33

G-protein contains GTPase domain which hydrolysis GTP into GDP, inactivating itself, and leaves adenylyl cyclase, inactivating it

Question 34

Describe the cellular response of glucagon

Answer 34

1. Glycogen phosphorylase activated which catalyse breakdown of glycogen (glycogenolysis) (gluconeogenesis) 2. Inhibits glycogen synthase needed for glycogenesis

Question 35

How does signalling pathway for insulin differ from that or glucagon ?

Answer 35

Type of receptor: - Tyrosine kinase - G-protein linked receptor Activation of receptor: - Cross-phosphorylation of tyrosine residues on cytoplasmic tails of receptor - activation of G-protein as GTP displaces GDP Signal transduction: - relay proteins bind to activated receptor and are activated. Relay proteins bind to and activate other kinases - G-protein moves to adenylyl cyclase converting ATP to cAMP. cAMP bind to activate protein kinase A

Question 36

What are the roles of 1. Glycogen synthase 2. Glycogen phosphorylase 3. Glucokinase

Answer 36

1. Glycogenesis (make glycogen) 2. Gluconeogenesis (make glucose) 3. Glycolysis (breakdown glucose)

Question 37

Properties on insulin and glucagon that slows the to perform their function

Answer 37

1. Complementary shape with ligand binding site of receptor 2. Globular proteins with hydrophilic R groups projected outwards. - allows them to be transported in the blood stream to different target cells