Lecture 18: Signalling through enzyme linked receptors

Question 1

What receptors are involved with intrinsic enzymatic activity?

Answer 1

Receptor tyrosine kinases
Receptor serine/threonine kinases

Question 2

What receptors are involved with linked enzymatic activity?

Answer 2

Cytokine receptors

Question 3

What are kinases?

Answer 3

Enzymes that transfer a phosphate to a protein for phosphorylation

Question 4

What are phosphatases?

Answer 4

Enzymes that remove phosphates from a protein

Question 5

How do protein kinases work?

Answer 5

Catalyse the covalent modification of amino acids with OH groups using a phosphate from ATP

Question 6

What is the role of phosphorylation and de-phosphorylation?

Answer 6

Molecular switches

Question 7

How does signal transduction from protein phosphorylation usually occur?

Answer 7

In a cascade

Question 8

How are RTK dimers stabilised?

Answer 8

Signal molecules

Question 9

What is the process of RTK activation?

Answer 9

1. Dimerisation brings intracellular kinase domains in contact
2. Kinases are activated
3. They phosphorylate each other on multiple tyrosines

Question 10

How does signalling using RTKs occur?

Answer 10

1. Phosphotyrosine residues make docking sites
2. Association with and activation of downstream signalling proteins in receptor tails
3. Generates signalling complex

Question 11

How does termination of RTKs occur?

Answer 11

1. Phosphate removal by protein tyrosine phosphatases
2. Receptor endocytosis and degradation in lysosome

Question 12

What is RAS?

Answer 12

Monomeric G protein that acts as a molecular switch downstream of RTK

Question 13

How does RTK activate RAS?

Answer 13

Causes RAS to bind to GTP
This activates it

Question 14

How does RTK activate RAS using GRB2/SOS?

Answer 14

1. Phosphorylated RTK attracts GRB2 to PM
2. GRB2 binds to SOS and activates it
3. SOS converts RAS-GDP to active RAS-GTP
4. This activates downstream pathways like MAPK

Question 15

What happens when MAPK phosphorylation causes phosphorylation of enzymes?

Answer 15

Alters cell metabolism
Alters response to stimuli

Question 16

What happens when MAPK phosphorylation causes phosphorylation of cytoskeletal proteins?

Answer 16

Altered cell shape

Question 17

What happens when MAPK phosphorylation causes phosphorylation of gene regulatory proteins?

Answer 17

Altered expression of many genes involved in cell survival proliferation migration and differentiation

Question 18

What is PI3K?

Answer 18

Phosphatidylinositol 3-kinase
Heterodimeric lipid kinase

Question 19

What is in the regulatory subunit of PI3K?

Answer 19

SH2 domain

Question 20

What is in the catalytic subunit of PI3K?

Answer 20

ATP binding site
Dual specificity phosphorylates

Question 21

What are the three stages of signal transduction through cell surface receptors?

Answer 21

Reception
Transduction
Response