Cell signalling 3

Question 1

rod photoreceptor provides

Answer 1

monochrome vision in low light

Question 2

Where is the rhodopsin GPCR

Answer 2

in membrane discs in the outer segment

receptors at the back of the eye with light coming in the opposite end

Question 3

Light signalling to the brain process

Answer 3

Light strikes GPCR receptors on the inner membrane, rhodopsin absorbs a photon
Receptor interacts with alpha transducin, activated and changes conformation and takes up GTP, releases GDP
Interacts with target protein cGMP phosphodiesterase, activated, which hydrolyses cGMP to 5’GMP
cGMP usually holds ion channels open, so when when it is removed the channels close- stops Na+ entering cell (across plasma membrane)
1mv membrane potential change, inhibitory nt not released so signals are transmitted to the brain

Question 4

Reversion to the resting state- switching off the signal: Rhodopsin GPCR

Answer 4

Chromophore retinal in photoisomerised from 11-cis to all-trans by absorbing a photon and needs to be replaced by a new 11-cis retinal
This is synthesised from vitamin A

Question 5

Reversion to the resting state: alpha transducin

Answer 5

Self inactivating G protein alpha subunit

GTPase activity hydrolyses GTP to GDP

Question 6

Reversion to the resting state: cGMP

Answer 6

Synthesis of cGMP from GTP by guanyl cyclase

Stimulated by low ca levels

Question 7

Signal amplification allows

Answer 7

detection of low light levels for sensitivity

Question 8

Adaption allows

Answer 8

detection of changes in light levels even in bright light
Due to many GPCRs being activated, closing many ion channels and ca cytoplasmic levels fall (along with Na)
Ca is needed to activate enzymes involved in amplification

Question 9

Receptor tyrosine kinase

Answer 9

Has intrinsic enzyme activity (unlike GPCR)- enzyme it contains is tyrosine kinase
Incl mitogens

Question 10

Mitogens

Answer 10

Meditate local/short range communication
autocrine/paracrine signalling
Act as signals for receptor tyrosinase kinase signalling
Act at low conc and high specificity for receptors

Question 11

Examples of mitogens

Answer 11

Insulin like growth factor- cell survival and proliferation
Platelet- derived growth factor- cell proliferation
Nerve growth factor- neuron survival

Question 12

Tyrosinase kinase receptor dimerisation

Answer 12

The inactive RTKs are monomeric- have to come together and function as a pair
Happens by the signal binding- holds the 2 copies together
When brought together the kinase activity is stimulated

Question 13

Autophosphorylation

Answer 13

Tyrosine kinases autophosphorylate one another/ cross phosphorylate
Addition of phospahtes incr activity of Tyrosine Kinases
Additional tyrosine residues in the receptor get phosphorylated

Question 14

Signal protein binding

Answer 14

Change in conformation around each phosphate allows docking of signalling proteins that initiate the next step of the signalling cascade
Become activated intracellular signalling proteins

Question 15

Signalling rapidly reversed by

more on this

Answer 15

phosphatase activity

Question 16

Adaption occurs due to

Answer 16

receptor internalisation and degradation

Question 17

Ras activation

Answer 17

Have activated RTK
Interaction of specific domain with adaptor protein
Adaptor protein interacts in turn with Ras-GEF which activates the Ras protein

Ras protein releases GDP, takes up GTP . Change in conformation means it can interact with the next protein and allow onward transmission of signal

Question 18

Reversal promoted by

Answer 18

interaction with Ras-GAP

GTPase activating protein (activates GTPase activity in Ras)

Question 19

Ras

Answer 19

monomeric GTPase (same as alpha subunit of GPCR)

Question 20

Ras stimulates

Answer 20

serine/ threonine kinase cascade

Question 21

How does activated RAs stimulate a cascade

Answer 21

interact with MAP kinases and activate them

Question 22

What does activation of MAP kinases cause

Answer 22

Promotes cell proliferation
Leads to phosphorylation of protein targets to cause changes in protein activity and phosphoryation of TFs to cause changes in gene expression

Question 23

All of the proteins are coded for by

Answer 23

oncogenes

Question 24

RTKs stimulate cell survival through

Answer 24

PI3-Kinase

Question 25

How does activation of PI3-kinase work and what does it trigger

Answer 25

PI3-kinase docks to activated RTK and becomes activated
Phosphorylates inositol phospholipids.
These (inositol phospholipids) act as a docking site for target proteins
eg protein kinase 1 and Akt
Protein kinase one phosphorylates Akt and protein kinase 2 interacts, resulting in the signal being relayed onward by activated Akt

Question 26

Akt inactivates

Answer 26

BAD protein by phosphorylation

Question 27

What does inactivation of BAD do

Answer 27

Prevents BAD interacting with Bcl2 like usual, to allow cell death by apoptosis

Phosphorylation of BAD releases active Bcl2 nad inactive bad, promotion of cell survival by inhibition of apoptosis

Question 28

Activated Akt can also activate

Answer 28

Tor

Question 29

Activation of mTOR

Answer 29

regulates cell growth
inhibition of protein degradation
Stimulation of protein synthesis
Leads to cell growth

Question 30

Importance of Ras/MAP-kinase pathway

Answer 30

outcome depends on cell type, often promotes cell proliferation
Ras neutralising antibodies can block cell proliferation
Ras gene is mutated in 30% of all human cancers
Ras and other members of the pathway are oncogenes and tumour suppressors

Question 31

Protein conformation switches

Answer 31

Used in cell signalling pathways

Protein kinase phosphorylates protein to activate, then protein phosphotase removes phosphate to switch protein off

GTP binds to replace GDP to switch protein on, GTP hydrolysis occurs to convert back to GDP bound form which is switched off

Question 32

Integration devices

Answer 32

Some signalling proteins

Only when they receive signal from multiple pathways is there a response