Week 4 - Cell Signalling

Question 1

What is Herceptin’s target

Answer 1

HER2

Question 2

What is salbutamol’s target

Answer 2

Cell surface receptor (beta 2 receptor)

Question 3

What is imatinib’s target (used to treat CML)

Answer 3

Intracellular protein tyrosine kinase (Bcr-Abl)

Question 4

What is bevacizumab’s target

Answer 4

VEGF which is the signal for angiogenesis

Question 5

In which 2 ways can biochemical signals be classified

Answer 5

Chemical structure and range of action (distance)

Question 6

Why is cell signalling important?
(3)

Answer 6

To coordinate development

To maintain normal physiological function

If signalling is abnormal, it can cause disease

Question 7

3 types of signalling molecules

Answer 7

Amino acid derivatives
-Adrenaline (modified aa)
- Oxytocin (peptide hormone)
- Insulin (insulin, growth hormone)

Steroid hormones (derived from cholesterol)
- Testosterone

Eicosanoids (derived from lipids)
e.g prostaglandin

Question 8

What is the name for long distance chemical signalling

Answer 8

Endocrine - via blood

Question 9

What is the name for chemical signalling between nearby cells

Answer 9

Paracrine

Question 10

What is the name for chemical signalling via cell:cell contact

Answer 10

Juxtacrine

Question 11

What is the name for chemical signalling from the same cell

Answer 11

Autocrine

Question 12

What are the 3 stages of signal transduction

Answer 12

Detection

Transduction

Response

Question 13

How do hydrophobic signal molecules reach their receptor

Answer 13

Through the membrane as they are hydrophobic

Question 14

Examples of hydrophobic signalling molecules

Answer 14

Steroid hormones - oestrogen/testosterone
Nitric acid (g)

Question 15

What is the steroid hormone’s mechanism of action

Answer 15

Steroid hormone diffuses through the membrane and binds directly to the intracellular receptor proteins

The hormone-receptor complex acts as a transcription factor which binds to DNA and alters gene expression

Question 16

Example of a hydrophobic signalling molecule

Answer 16

Steroid hormone

Question 17

Example of a hydrophilic signalling molecule

Answer 17

Insulin/adrenaline

Question 18

What must hydrophilic signalling molecules use to cause a response

Answer 18

They must use a cell surface receptor protein

Question 19

What are the 3 main types of cell surface receptors and give an example

Answer 19

Ion-channel-linked
(glutamate neurotransmitter)

G-protein-linked (GPCR)
(adrenaline, serotonin)

Enzyme-linked
(RTK, growth factors, insulin)

Question 20

Describe the mechanism of an ion-channel-linked receptor

Answer 20

Signal molecule binds to receptor on receptor. Ion flow into cell changes electrical properties of the cell

Question 21

Describe the mechanism of a G-protein-linked/coupled (GPCR)

Answer 21

Signal molecule binds to activated G protein which then activates enzyme that passes on signal into cell

Question 22

Describe the mechanism of the enzyme-linked receptor

Answer 22

Signal molecule binds to receptor, bringing the receptor together (dimerisation) which then goes on to activate an intracellular enzyme

Question 23

Which enzyme phosphorylates molecules

Answer 23

Kinase

Question 24

Which enzyme dephosphorylates molecules

Answer 24

Dephosphatase

Question 25

Outline the mechanism of the enzyme-linked receptor RTK (receptor tyrosine kinase)

Answer 25

Signalling molecule binds to receptor, receptor is pulled closer together, dimerisation occurs. Tyrosine is phosphorylated by kinase, which act as a docking station for intracellular proteins

Question 26

Two methods of transduction

Answer 26

Enzyme cascades Second messengers

Question 27

When are MAPK cascades often activated

Answer 27

In response to RTK activation by growth factors (receptor tyrosine kinases) e.g EGF

Question 28

What type of cascade is an MAPK

Answer 28

An enzyme cascade

Question 29

What is often activated in response to growth factor RTK activation e.g by EGF

Answer 29

MAPK cascades

Question 30

What happens before an MAPK cascade after phosphorylation of tyrosine occurs

Answer 30

Relay proteins such as Grb/Sos activate the proto oncogene RAS MAP kinase cascade is activated Signal is amplified

Question 31

What is a second messenger

Answer 31

Small molecule produced in large amounts inside the cell after receptor activation

Question 32

Give an example of a second messenger

Answer 32

cAMP

Question 33

How do second messengers result in cellular response

Answer 33

Signal molecule binds, G protein is activated and activates the Enzyme. Enzyme converts ATP into lots of cAMP. cAMP binds to Molecule callsed protein kinase A and activates it. The kinase Can then be used to phosphorylate lots of different target proteins.

Question 34

Name 3 other second messengers other than cAMP

Answer 34

DAG which activates PKA IP3 which causes Ca2+ release Ca2+ which activates Ca-dependent enzymes including CaMKs

Question 35

What is the typical pairings of GPCRs/RTKs and second messengers/MAPK

Answer 35

GPCRs usually activate second messengers RTKs usually activate MAPK cascades

Question 36

Name 4 different responses possible as a result of signal molecule reception and transduction

Answer 36

Gene expression Protein activity Protein binding Protein localisation

Question 37

What do drugs ending in AB do

Answer 37

Use antibodies to inactivate them and block the signalling pathway

Question 38

What do drugs ending in IB do

Answer 38

They use small molecule kinase inhibitors to block the signal pathway

Question 39

Which pathways are usually overactive in cancer

Answer 39

Growth factor Receptor Tyrosine Kinase

Question 40

What does herceptin target

Answer 40

It targets the factors that produce the human epidermal growth receptor

Question 41

What does Bevacizumab target

Answer 41

VEGF (vascular endothelial GF) which prevents angiogenesis

Question 42

What does Gefitinib target

Answer 42

Iti inhibits EGFR receptor (lung cancer)

Question 43

When G protein is active, which nucleotide is bound to alpha subunit

Answer 43

GTP

Question 44

When G protein is inactive, which nucleotide is bound to alpha subunit

Answer 44

GDP

Question 45

How is G protein deactivated

Answer 45

GAP protein hydrolyses G protein into GDP

Question 46

Effector proteins produced as a result of activated G protein can do what

Answer 46

Can activate or inhibit targets, directly or indirectly

Question 47

During glucose release caused by adrenaline, what are the two pathways that can result from phosphorylated kinase activator

Answer 47

Activation of kinase which phosphorylase glycogen into glucose OR Activation of glycogen synthase which phosphorylase glycogen synthase which de phosphorylases glucose into glycogen

Question 48

What happens when adrenaline no longer binds to receptor, this triggers what?

Answer 48

This causes the G protein subunit to no longer be activated. Phosphodiesterase removes the residual cAMP

Question 49

Can signalling molecules activate singular pathways or multiple

Answer 49

They can activate multiple!

Question 50

How is specificity in signalling achieved?

Answer 50

The factors that contribute to variation are: The type of receptor The G protein involved The effector enzyme The second messenger produced

Question 51

Why shouldn't you give a patient with heart problems beta blockers if they also have asthma?

Answer 51

you don’t want to give a patient with heart condition AND asthma beta blockers because it will have an antagonistic effect on bronchodilation!