Membrane structure and function III

Question 1

What are some types of tyrosine kinase receptors

Answer 1

1. Insulin
2. Epidermal growth factor (EGF)
3. Platelet derived growth factor (PDGF)

Question 2

What does Jak-STAT signalling regulate

Answer 2

1. Growth hormone

2. Interferon

Question 3

What is a type of serine/threonine kinase receptor

Answer 3

TGF beta receptor

Question 4

How are tyrosine receptors dimerised

Answer 4

1. The 2 identical receptor molecules will dimerise after ligand binding makes a conformational change
2. When the 2 molecules come together, signalling proteins cross link the receptors

Question 5

How do tyrosine receptors become phosphorylated

Answer 5

The dimerisation brings together elements of the molecules, allowing them to modify each other
Phosphorylation occurs on specific tyrosine residues on the receptors through auto-phosphorylation

Question 6

What happens after phosphorylation of the dimerised receptors

Answer 6

This creates further conformational changes that gives the receptor a docking site for other proteins
This could induce more phosphorylation and more protein binding and the chain reaction goes on

Question 7

Activated tyrosine receptor; RAS protein pathway

Answer 7

1. Grb-2 binds to the SH2 domain of the activated receptor causing a conformational change
2. This allow Ras GEF to binds to the Grb-2 on its SH3 domain
3. Ras GEF phosphorylates GDP bound on the RAS-GDP complex, making it a GTP
4. Activated RAS protein will initiate a a number of different signals

Question 8

Activated tyrosine receptor; PKB pathway

Answer 8

Tyrosine phosphorylation will cause PI 3-Kinase to be activated
This phosphorylates PIP2 to PIP3
PDK1 can bind to PIP3, causing it to activate and phosphorylate protein kinase B (PKB)

Question 9

What will activated protein kinase B do

Answer 9

It will dissociate and activate other molecules in the cytosol

Question 10

Where is the insulin receptor located and what does it do

Answer 10

Acts on the liver and muscle to reduce blood glucose

Question 11

Whats the structure of the insulin receptor

Answer 11

Consists of 2 alpha and 2 beta subunits linked by disulphide bridges

Question 12

What does binding on the insulin receptor cause

Answer 12

Auto-phosphorylation of the 2 beta subunits

Question 13

What does phosphorylation of the insulin receptor cause

Answer 13

Activation of a large protein substrate - IRS
activated IRS activates PI 3-Kinase, which activates PKB
activates PKB will have effects of synthesis of glycogen and proteins

Question 14

How are activated proteins disabled

Answer 14

Phosphatases are activated as a result of the receptor activation
They will remove phosphates therefore deactivating the proteins

Question 15

How is PKB deactivated

Answer 15

P10

Question 16

How are GTP binding proteins deactivated

Answer 16

They have intrinsic GTPase activity so deactivate over time

Question 17

How is RAS protein activation regulated

Answer 17

Guanine nucleotide exchange factor will take inactive GDP and replace it with GTP
Activation of RAS will activate GTPase activating protein (GAP)
This will increase the GTPase activity on the RAS protein therefore speeding up the dephosphosphoryaltimn of GTP to GDP therefore deactivating the RAS protein

Question 18

How can mutations in key regulatory mechanisms lead to cancer

Answer 18

Loss of GTPase activity or phosphatase activity could cause unregulated activation
Also over expression of EGF receptors can lead to breast cancers

Question 19

Jak-STAT signalling pathway process

Answer 19

Ligand binding to the receptor causes Jaks to cross phosphorylate each other on tyrosines
Activated Jaks phosphorylate receptors on tyrosine
STAT1 and STAT2 dock on phosphotyrosines
Jaks phosphorylate STAT1 and STAT2
STATs disscoate from the receptor and dimerise via SH2 domain
Dimer will move into the nucleus and cause an increase in specific genes transcription

Question 20

Smad-dependant signalling pathway

Answer 20

TGF-beta will initially bind to the type II TGF-beta receptor
This will allow for the association of type I TGF-Beta receptor to the type II
This will lead to the phosphorylation of type I
Smad 2 and smad 3 will be phosphorylated and activated
This will activate smad 4
A heterodimer will form
This heterodimer will go into the nucleus and it will regulate gene expression