L41- Cell signalling (enzyme linked receptor)

Question 1

what is an enzyme-linked receptor?

Answer 1

• they possess an in-built receptor

- these enzymes are acivated upon ligand binding

Question 2

what do enzyme-linked receptors do?

Answer 2

-They relay the extracellular signal to the nucleus by a sequence of interaction that eventually switch on specific transcription factors, altering gene expression in the cell

Question 3

what are the different enzyme-linked receptor structure?

Answer 3

• ligan-binding domain
• transmembrane domain
• intracellular catalytic domain

Question 4

what is the role of the Ligand-binding domain?

Answer 4

• Extracellular to allow easy access for ligands

- Strong affinity for specific ligands

Question 5

what is the role of the transmembrane domain?

Answer 5

• Contains a series of hydrophobic amino acids

- Tethers the receptor to the cell membrane

Question 6

what is the role of the intracellular catalytic domain?

Answer 6

-Either intrinsic to the receptor or tightly bound via
the cytosolic domain
-Majority are kinases

Question 7

what is kinase?

Answer 7

-it is an enzyme that catalyses the transfer of a phosphate from ATP>to a specific protein.

Question 8

what enzyme carries out phosphorylation?

Answer 8

kinase

Question 9

what enzyme carries out dephosphorylation?

Answer 9

phosphatase

Question 10

what are some downstream effects of kinase-linked receptors?

Answer 10

• cell growth
• apoptosis
• tissue repair
• immune response

Question 11

explain 2 way of a signal-mediated response?

Answer 11

either:
-receptor is phosphorylated leading to the kinase then getting phosphorylated>TF
or
-When ligand attaches to the

Question 12

name one type of major enzyme-linked receptor?

Answer 12

• Receptor tyrosine kinase (RTK)
• receptor serine/threonine kinase
• tyrosine kinase associated receptors

Question 13

how does a receptor tyrosine kinase work?

Answer 13

• signal molecule will bind to signal binding site on receptor causing a conformational change
• this change will bring the 2 polypeptides together to form a dimer formation
• this activates the tyrosine kinase regions
• the kinase allows the tyrosine to be phosphorylated using ATP forming a phosphorylated dimer
• relay protein such as SH2 binds to the phosphotyrosine and conformational change leading to signal transductional pathway for cellular response.

Question 14

What is Src homology 2 (SH2) domains?

Answer 14

they bind to phosphotyrosine residues, they are very specific

Question 15

how many types of receptor serine/theronine kinase is there?

Answer 15

2: type I AND TYPE II

Question 16

What is receptor serine/theronine kinase type I?

Answer 16

 Inactive unless in complex with type II receptors
 Do not interact with ligand dimers
 Contain conserved sequences of serine and threonine residues near to their kinase domains

Question 17

What is receptor serine/theronine kinase type II?

Answer 17

 Constitutively active kinase domains (even in the absence of
the bound ligand).
 Able to phosphorylate and activate the type I receptor.

Question 18

how does a receptor sarin/threonine kinase work?

Answer 18

-type I is kept inactive by a portion of its cytosolic domain that blocks its kinase activity
-BMP ligands bind as dimers to type II receptor
type II receptors thenbind and phosphorylate type I receptor this removes the inhibition of type I kinase activity
-type I receptor then phosphorylate Smad transcription factors allowing it to enter the nucleus to repress or activate target gene expression.

Question 19

what is the main ligand for tyrosine kinase associated receptors?

Answer 19

cytokines

Question 20

what happens during a tyrosine kinase-associated receptor response?

Answer 20

• cytokines is the main ligand that binds to the tyrosine kinase-associated receptor to 2 receptor monomers simultaneously
• this brings them together
• 1 kinase phosphorylates the other in an area called the the activation lip- JAK
• JAK moves out of the active site and binds to ATP leading to more kinase activity
• enhanced kinase phosphorylates more tyrosine residues on the intracellular portion of the receptor
• phosophtyrosines serve as docking sites for SH2 domain containing proteins like STAT