Cell Communication And Proliferation

Question 0

What do protein kinases do?

Answer 0

Phosphorylates protein on serine, threonine or tyrosine residues

Question 1

Name the different ranges signals can act

Answer 1

Endocrine- via blood stream; hormones
Paracrine- local signalling to neighbouring cells; histamine, NO
Autocrine- cell responds to it’s own signal
Neuronal; neurotransmitters
Contact dependent- membrane bound signal molecules; delta in a notch receptor

Question 2

What is a molecular switch?

Answer 2

GTPases cycle between active GTP bound state and inactive GDP bound state
The active form us able to activate downstream effector proteins

Question 3

Name some cell surface receptors

Answer 3

Ion channel coupled receptor- opens/closes in response to an extracellular signalling molecule, results in change of membrane potential
G protein coupled receptor- binding of ligand causes conformational change resulting in the activation of a G protein on the intracellular leaflet of the plasma membrane, can activate enzymes or ion channels
Enzyme-coupled receptors- signal bonds to extracellular receptor domain that causes a change in confirmation that activates the intracellular catalytic domain

Question 4

What is the active form of a G protein?

Answer 4

A conformational change in the alpha subunit that swaps GDP for GTP and is activated
The alpha subunit dissociate from the gamma-bate subunit complex
The activated alpha subunit and beta-gamma complex can now activate downstream signals

Question 5

Which enzyme generates cAMP?

Answer 5

Adenylyl cyclase

Question 6

What enzyme converts cAMP to AMP?

Answer 6

Cyclic AMP phosphodiesterase

Question 7

What is the role of tyrosine kinase in cell proliferation?

Answer 7

Binding of a growth factor molecule dimerises the tyrosine kinase and activates the kinase domains- transphosphorylation
Now the phosphorylase r tyrosine can recruit an adaptor protein eg. Grb2 which can recruit a Ras activating protein which promoted the exchange of GDP for GTP in Ras

Question 8

Describe the MAP kinase pathway

Answer 8

Activated membrane associated Ras brings Raf to the membrane and actives it
Raf activates Mek
Mek activates Erk
Mek and Erk migrate to the nucleus and activate proteins and transcription factors that dive entry into the cell cycle

Question 9

What is HER2?

Answer 9

An epidermal growth factor receptor family of receptor tyrosine kinase
Amplification of HER2 is found in many breadth cancer cells

Question 10

Name the different Cdks and their cyclins

Answer 10

G1-Cdk- cyclin D + cdk4, cdk6
G1/S-Cdks- cyclin E + cdk2
S-Cdk- cyclin A+cdk2, cdk1
M-Cdks- cyclin B+cdk1

Question 11

What are pre-RCs?

Answer 11

Pre-replicative complexes they form in DNA replication origins during G1 made of ORC and DNA helicase
S-Cdk phosphorylates and activates DNA helicase that opens up the origin

Question 12

What is Wee1 kinase?

Answer 12

Phosphorylates and inactivates the cdk1 subunit of M-cdk

Question 13

How are securin and seperase involved in the Cell division?

Answer 13

Securin must be ubiquitated and degraded to free seperase
APC can do this once all the chromosomes are connected to a mitotic spindle by kinetochores and us activated
Seperase breaks down cohesion complexes that hold sister chromosomes together so they can be pulled apart in anaphase

Question 14

What does p53 do in the presence of damaged DNA?

Answer 14

If damage to DNA is detected p53 bonds to the regulatory region of p21 gene
p21 inhibits G1/S-cdk and S-cdk

Question 15

What are caspases?

Answer 15

Required for apoptosis
Family of highly specific intracellular cysteine aspartate proteases
They are activated by proteolytic cleavage

Question 16

How do importins get cargo in and out of the nucleus?

Answer 16

Ran-GTP binding displaces cargo and release of Ran-GDP loads cargo
Ran-Gap turns GTP to GDP
Ran-Gef exchanges GDP for GTP

Question 17

Which protein targets the translational complex to the ER membrane?

Answer 17

Signal recognition particle

Question 18

What does a N-linked oligosaccharide do?

Answer 18

Transferred by oligosaccharyl transferase to an aspartate side chain on a newly translated protein as it’s fed through the ER membrane
It influences the protein conformation and solubility

Question 19

Name some different coats used on vesicles

Answer 19

Clathrin coats transport vesicles from the plasma membrane and between endosomal and Golgi compartments
COP1 bud from Golgi compartments
COP2- bud from the ER

Question 20

What are SNAREs?

Answer 20

Soluble N-ethyl malimide-sensitive factor Attachment REceptor
V-SNAREs are on vesicle surfaces
T-SNAREs are on the target compartment

Question 21

What is the name of the protein that contributes to the specificity of transport vesicle fusion?

Answer 21

Rabs- carried by the transport vesicle

Question 22

What is the difference between constitutive and regulated secretory pathway?

Answer 22

Constitutive- unregulated fusion with the membrane
Regulatory- regulated by an intracellular signalling pathway as a response to an external signal such as a hormone or neurotransmitter

Question 23

Describe proteasome structure

Answer 23

20S core- barrel shaped made of 14 subunits (7 alpha, 7 beta) where proteolysis occurs; substrates cleaved at the C-terminus to an aromatic or basic amino acid residue or to glutamate
Two 19S regulatory subunits- lid and base

Question 24

Describe ubiquitination

Answer 24

1) E1 activates ubiquitin; ATP dependent
2) E2; ubiquitin carrier- accepts ubiquitin from E1
3) E3 ; ubiquitin ligase transfers ubiquitin to the acceptor protein

Question 25

What does HIF-alpha do?

Answer 25

If oxygen is absent it activates it’s target genes and starts vascularisation
If present it is triple ubiquitinated and broken down by a proteasome

Question 26

What are PCSKs?

Answer 26

Proprotein convertases
Recognises basic amino acids and cleaves at the C-terminus to Arginine
Responsible for the maturation of pro-insulin
Exploited by viruses to mature their envelope glycoproteins