Cell Signalling Flashcards
What are the stages of cell signalling ?
- Ligand-receptor interaction
2, signal transduction - Cellular response
Describe ligand-receptor interaction
Specific ligand binds to specific ligand binding site on the receptor protein, causing conformational change and activating the receptor.
What are the types of receptors ?
- Tyrosine kinase receptor
- G-protein linked receptor
- Ion channel receptor
Where are these receptors found ?
What does this imply about their nature ?
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
What happens after receptor is activated from ligand-receptor interaction ?
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
What is dimerisation ?
When receptor is split into 2 but close together when ligand binds
Describe signal transduction and how it’s done ?
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
Describe phosphorylation and dephosphorylation of proteins in signal transduction
Phosphorylated by kinase
Dephosphorylated by phosphatase
Protein kinase added phosphate group from ATP to inactive protein, causing conformational change, activating the protein.
(Generating ADP)
Describe the role of second messengers in signal transduction
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
Explain cAMP as a second messanger
What are the types of cellular response ?
- Cytoplasmic response
- Nuclear response
Describe cytoplasmic response
Change in activity of enzymes and proteins in cytoplasm
E.g: inhibition, synthesis
Describe nuclear response
Specific gene coding for the synthesis of certain enzymes or proteins switched on or off
What allows signal amplification ?
- Phosphorylation cascade
- Second messengers
How does phosphorylation cascade lead to signal amplification ?
Each activated relay protein can activate multiple molecules of a downstream relay protein
How does second messengers lead to signal amplification ?
Each active enzyme catalyses the formation of many second messnagers.
Each second messengers can bind to and activate a specific protein
What type of receptor is insulin ?
Tyrosine kinase receptor
What cells detect how increase in blood glucose ? And what do they secrete ?
B cells of the islet of langerhans in pancreas
Secrete insulin
Why are insulin and glucagon receptors found on cell surface membrane and not in the cell
Insulin and glucagon are globular protein with hydrophilic R groups pointed towards the exterior cannot pass through hydrophobic core of csm
What is the target cells of insulin ?
Liver and muscle cells
Outline the ligand-receptor interaction stage of Insulin
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
Describe the signal transduction pathway of insulin ?
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）
Describe cellular response of insulin pathway
- Vesicles in the cytoplasm that contain glucose carriers move and fuse to cell surface membrane, increasing rate of glucose uptake via facilitated diffusion.
- Glucokinase is activated, phosphorylated glucose into glucose-6-phosphate for glycolysis
- Stimulates glycogenesis (glycogen synthase activated) , ihhibits glycogenolysis (glycogen phosphorylase inhibited) , inhibits gluconeogenesis
What is
1. Glycolysis
2. Glycogenesis
3. Glycogenolysis
4. Gkuconeogenesis
- Break down of glucose
- Synthesis of glycogen
- Breakdown of glycogen
- Synthesis of glucose
What type of receptor glucagon receptor ?
G-protein linked receptor
What cells detect how decrease in blood glucose ? And what do they secrete ?
a cells in islet of langerhans in pancreas
Secrete glucagon
What are the target cells of glucagon ?
Liver cells
Outline ligand-receptor interaction stage of glucagon
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.
Describe the structure of glucagon
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
Outline signal transduction pathway of glucagon
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.
Is there amplification in phosphorylation of PKA ?
No. Since there’s only activation of 1 kinase (phosphorylase kinase)
Why are changes in adenylyl cyclase and G-protein only temporary ?
G-protein contains GTPase domain which hydrolysis GTP into GDP, inactivating itself, and leaves adenylyl cyclase, inactivating it
Describe the cellular response of glucagon
- Glycogen phosphorylase activated which catalyse breakdown of glycogen (glycogenolysis) (gluconeogenesis)
- Inhibits glycogen synthase needed for glycogenesis
How does signalling pathway for insulin differ from that or glucagon ?
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
What are the roles of
1. Glycogen synthase
2. Glycogen phosphorylase
3. Glucokinase
- Glycogenesis (make glycogen)
- Gluconeogenesis (make glucose)
- Glycolysis (breakdown glucose)
Properties on insulin and glucagon that slows the to perform their function
- Complementary shape with ligand binding site of receptor
- Globular proteins with hydrophilic R groups projected outwards.
- allows them to be transported in the blood stream to different target cells
