Receptor mechanism III

Question 1

What are growth factor receptors predominately?

Answer 1

• Predominantly single transmembrane domain receptors

Question 2

What does the activation of growth receptors lead to?

Answer 2

Activation of receptor Kinases and multiple signalling pathways

Question 3

Examples of tyrosine receptor kinase

Answer 3

Insulin

EGF or PDGF

Question 4

What are jak/stat and what are they involved in?

Answer 4

○ chain of interactions between proteins in a cell
○ Growth hormone

Interferon

Question 5

Example of serine threonine receptor kinase

Answer 5

○ TGFβ

Question 6

What are enzyme linked receptors involved in the regulation of?

Answer 6

○ Cell growth 
○ Division
○ Differentiation
○ Survival
○ Migration

Question 7

Consequences of inappropriate activation of enzyme linked receptors

Answer 7

• Inappropriate activation is associated with disease particularly cancer

Question 8

What does dimerization do when it comes to tyrosine activity?

Answer 8

• Dimerization brings two receptor molecules together allowing phosphorylation of specific tyrosine residues

Question 9

Can all tyrosine residues be phosphorylated?

Answer 9

• Not all tyrosine residues can be phosphorylated

Question 10

How are phosphotyrosine recognized and what does it lead to?

Answer 10

• Phosphotyrosine together with surrounding amino acids are recognised by SH2 domains of other proteins allowing them to bind and undergo activaiton

Question 11

Result of the activation of tyrosine kinase receptors

Answer 11

• Activation of tyrosine kinase receptors activates multiple pathways

Question 12

What do insulin receptors act on?

Answer 12

• Acts on liver and muscle to reduce blood glucose

Question 13

What do insulin receptors consist of and how are they linked?

Answer 13

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

Question 14

What does the binding of insulin result in?

Answer 14

• Binding of insulin results in auto-phosphorylation of 2beta subunits

Question 15

What does the activation of receptors lead to?

Answer 15

• Activation of receptors leads to activation family of small protein substrates called IRS

Question 16

What does activated IRS activate?

Answer 16

○ IRS activates PI 3-kinase which activates PKB

Question 17

What other substrates do insulin receptors recruit?

Answer 17

• Insulin receptor substrate also recruits other proteins such as Ras and Phospholipase C

Question 18

What leads to the inactivation of receptor kinases?

Answer 18

• De-phosphorylation leads to inactivation

Question 19

What are activated as a result of receptor activation?

Answer 19

Phosphates are activated

Question 20

An example of a small G protein

Answer 20

Ras is one of a number of small G protein

Question 21

What are small G proteins related to?

Answer 21

• Related to Gα subunit of cAMP

Question 22

What are bound to small G proteins

Answer 22

Inactive GDP

Question 23

When activated, what happens to small G proteins?

Answer 23

When active, it is replaced by GTP helped by GEF

Question 24

What are small G proteins required for?

Answer 24

Growth, differentiation and cell motility

Question 25

What activity do small G proteins contain?

Answer 25

• Contains GTPase activity, slow de-phosphorylation helped by GAP

Question 26

What is slow de-phosphorylation helped by?

Answer 26

Helped by GAP

Question 27

In how many percent of human tumors is mutated Ras found in?

Answer 27

30% of human tumors

Question 28

What does the activity of Ras do?

Answer 28

Change GDP to GTP

Question 29

What does activated Ras interact with?

Answer 29

Other proteins including Raf

Question 30

What are activated Ras enhanced by?

Answer 30

Enhanced by GEF

Question 31

What is activated Ras the docking site for?

Answer 31

Activated Ras is docking site for GTPase

Question 32

What does activated GTPase lead to the removal of and what happens to the interaction between Ras and Raf/

Answer 32

• Activated GTPase leads to removal of phosphate to form GDP

○ RAS and Raf fall apart and is inactivated

Question 33

What can mutations in key regulatory mechanism lead to ?

Answer 33

Can lead to cancer

Question 34

What is Ras in cancers and what does it lead to?

Answer 34

Ras in cancers is mutated and leads to the loss of activity of GTPase

Question 35

What does mutations in phosphatases lead to

Answer 35

It leads to the loss of phosphatases activity

Question 36

Main issues in breast cancer

Answer 36

Over expression in breast cancer

Question 37

What does Herceptin target and what is it used for?

Answer 37

Targets a member of the EGF receptor family and used for the treatment of some cancers

Question 38

What do Jaks do to each other on tyrosines

Answer 38

Jaks cross phosphorylate each other on tyrosines

Question 39

What do activated jaks do to receptors on tyrosine?

Answer 39

They phosphorylate receptors on tyrosines

Question 40

What do STATS dock on to and what happens to them there?

Answer 40

Dock on phosphotyrosines and jaks phosphorylates them

Question 41

What is STAT?

Answer 41

STAT is a transcription factor

Question 42

What do STATs do once they’re phosphorylated?

Answer 42

STATs dissociate from the receptor and dimerize via SH2 domain

Question 43

What do the dimers of STAT do?

Answer 43

• Dimer of STAT will bind to specific region of DNA and stimulate transcription of specific protein

Question 44

What activates the smad-dependent signalling pathway?

Answer 44

TGF-beta

Question 45

Basic overview of the smad-dependent signalling pathwat

Answer 45

• Receptor dimerizes
• Allows phosphorylation
• Smad 2 and 4 phosphorylated
• These then dissociate and are recognised and activated by Smad 4
• This will form a dimer that enters the nucleus and bind to specific regions of DNA leading to the transcription of specific genes.