Cell signals and responses

Question 1

Types of cell communication

Answer 1

Remote signalling by secreted molecules
Contact signalling by membrane bound molecules (cell surface receptors on one cell bond to cell surface receptors of another cell)
Contact signalling via gap junctions

Question 2

Endocrine signalling

Answer 2

Secreted

Hormone produced, enters bloodstream and is carried to target cell

Question 3

Paracrine signalling

Answer 3

Secreted

Local chemical mediator released, acts on cells in immediate environment (e.g. cytokine)

Question 4

Autocrine signalling

Answer 4

Secreted

On itself

Question 5

Synaptic signalling

Answer 5

Secreted

Neurotransmitters released at synapses, diffuse to post-synaptic target cell

Question 6

Order of cell signalling

Answer 6

Signal –> reception –> transduction –> response

Question 7

Signal (outside)

Answer 7

Growth factors
Hormones
ECM
Chemicals
Proteins
Sugars
Synaptic

Question 8

Cell responses to signals

Answer 8

Growth, cell division
Differentiation
Metabolism (faster or slower)
Apoptosis (tells cell to die)
Gene transcription
Secretion
Contract/ relax
Membrane charge (can generate a.p)
Migration (often towards signal e.g. chemokine)

Question 9

How is transduction caused?

Answer 9

Signal –> cell surface receptor –> transduction

Question 10

Examples of transduction

Answer 10

Amplification, phosphorylation cascades, secondary messengers

Question 11

Intracellular receptors

Answer 11

Hydrophobic: can pass through plasma membrane
Transported into nucleus
Response: influence gene transcription
e.g. steroids, NO

Question 12

Types of membrane receptors

Answer 12

G-protein linked
Tyrosine kinases
Enzyme linked
Ion channels

Question 13

Monomeric (small) G-proteins

Answer 13

Ras
Family: H-Ras, K-Ras, N-Ras
Function controlled by GDP/ GTP cycle
Stimulates cascade of kinases (effectors)
Proliferation, differentiation, cell death

Question 14

What does mutation do to Ras

Answer 14

Makes Ras insensitiveto GTPase activation proteins (active for longer i.e. on all the time)

Question 15

Where are Ras mutations found

Answer 15

in ~30% of all tumours

Question 16

G-protein coupled receptors

Answer 16

Integral trans-membrane proteins
Receptor occupation promotes interaction with G-protein
Promotes exchange of bound GDP for GTP
Activates G protein (α subunit) which leaves receptor
Initiates signalling through secondary messengers
-another way of switching on/ off protein

Question 17

Why is cell signalling important?

Answer 17

For adaptation (e.g. to changes in environment), co-ordination and regulation

Question 18

What are endocrine hormones produced by?

Answer 18

Endocrine glands

Question 19

Do cytokines last long?

Answer 19

Have very short half-life, works for short time

Question 20

Two potential routes of signal to cell

Answer 20

Signal –> internal cell receptor

Signal –> cell surface receptor –> signal transduction

Question 21

Testosterone: hydrophilic or hydrophobic?

Describe pathway

Answer 21

Hydrophobic - can pass through cell membrane
Intracellular receptor
Binds to hormone-receptor coplex in cytoplasm, transported into nucleus, gene transcription altered, mRNA produced, new protein

Question 22

Example of post-translational modification. What does this do to protein

Answer 22

Phosphorylation (by kinase enzyme)
Phophorylation is like an on/off switch - big charge change
E.g. serine / threonine/ tyrosine

Question 23

How many times do G-protein coupled receptors cross membrane

Answer 23

7 times

Question 24

Are G-protein coupled receptors specific?

Answer 24

Yes, very. Won’t recognise other molecules

Question 25

LOOK AT WORD DOC

Answer 25

LOOK AT WORD DOC

Question 26

How many types of G-proteins

Answer 26

2 - one that associates with receptors - one that doesn't interact with receptors and floats around in cytoplasm (monomeric)

Question 27

Receptor tyrosine kinases

Answer 27

Dimerise upon ligand binding Have intrinsic enzymatic activity Puts phosphate from ATP on tyrosine (autophosphorylation) Bind src homology-2 (SH-2) proteins Initiates series of phosphrylation reactions

Question 28

What can complicated signal cascades do

Answer 28

Amplify signal | Lots of different levels to regulate process (fine tuning)

Question 29

Example of a transduction cascade

Answer 29

Mitogen activated protein (MAP) kinase system

Question 30

Enzyme linked receptors

Answer 30

Cytokine receptors - no intrinsic activity but associates with enzymes involved in phosphorylation - JAKs - rapid signal by shortcut system to nucleus by STATs

Question 31

Ion channels

Answer 31

Receptor is ion channel Ligand (e.g. neurotransmitter) binds to and opens channel (some voltage gated) Response: influx of Na+, change in membrane potential, a.p.

Question 32

Secondary messengers

Answer 32

Small molecules | Bind and activates other molecules

Question 33

Examples of secondary messengers

Answer 33

Cyclic adenosine monophosphate (cAMP) Inositol triphosphate (IP3) Ca2+ Diacylglycerol

Question 34

Control of signalling

Answer 34

Pathway leads to single response Pathway branches leading to 2 responses Cross-talk occurs between 2 patways (e.g. growth factor signalling) Different receptor leads to diff response

Question 35

Example of control of signalling

Answer 35

Inhibition by protein phosphatases

Question 36

Example of specificity of signal

Answer 36

``` Fibroblast growth factor receptor (FGFR) stimulation: -in fibroblasts - proliferation -in neuronal cells - differentiation Cellular compartmental isation e.g. STAT Scaffold proteins ```

Question 37

Scaffold proteins

Answer 37

Acts like enzyme in cytoplasm - makes reaction much more likely to happen

Question 38

Difficulty with therapeutic targets for cancer

Answer 38

If you target cells that are growing, will also target normal cells as well

Question 39

Therapeutic targets

Answer 39

Cell signalling transmits mitogenic and survival signals Over-expression in cancer - MAPK, PI3K Constitutive expression - transformation Activating mutations of G subunits and receptors Specific inhibitors - PD184352 (MEK) reduce tumour growth by up to 80% PTEN a tumour suppressor is a IP3 phosphatase

Question 40

What is the most important signalling molecules to target for tumours?

Answer 40

Epithelial growth factor receptors (most tumours are epithelial)

Question 41

Monomeric G-proteins and GDP/ GTP cycle

Answer 41

Inactive when bound to GDP | Phosphorylated (using ATP) to become bound to GTP --> active