Cell Signalling

Question 1

What are the 7 types of cell receptors for signalling?

Answer 1

1. G protein coupled receptors
2. Receptor tyrosine kinases
3. Serine-threonine kinases
4. Hedgehog signalling
5. Wnt signalling
6. EPH signalling
7. Notch-delta signalling

Question 2

What are the subunits which form the G protein coupled receptor?

Answer 2

The 3 subunits are alpha, beta and gamma.

Question 3

What happens when a signalling molecule binds to the G protein coupled receptor?

Answer 3

When inactive it is bound to GDP.

Once it becomes activated a conformational change takes place and allows GDP to unbind and GTP to bind.

Question 4

Which subunit is released and causes the signal transduction activity?

Answer 4

Alpha subunit

Question 5

What are the 2 main responses caused when the G protein coupled receptor is activated?

Answer 5

1. Activating adenylyl cyclase to form cAMP.

2. Activating phospholipase C beta which allows inositol triphosphate to bind to reservoirs and calcium to be released.

Question 6

What happens when the ligand binds to the tyrosine kinase receptor?

Answer 6

It promotes dimerization and phosphorylation of the tyrosine kinase on adjacent receptor.
It allows the binding of other molecules which will allow Ras to become activated.

Question 7

How is Ras activated?

Answer 7

Process is accelerated and modulated by GEF which binds to Ras GDP complex and allows GDP to disassociate and GTP to bind to Ras.

Question 8

What allows the dephosphorylation of Ras?

Answer 8

GAP (GTPase activating protein)

Question 9

What is the main role of tyrosine kinase receptors?

Answer 9

Phosphorylates proteins downstream which lead to proliferation and cell fate determination.

Question 10

What happens when the BMP ( bone morphogenetic protein) dimer binds to the BMP receptor in serine threonine kinase?

Answer 10

It allows subunit 2 to phosphorylate subunit 1. Subunit 1 phosphorylates the Smad protein which binds another Smad to form a transcriptional regulatory complex.
This enters nucleus and activates/represses target genes.

Question 11

What happens in the absence of Hedgehog?

Answer 11

Patched inhibits smoothened which leads to TF Ci being held in the cytoplasm.
Ci associates with smoothened, Cos2, Fu and another protein complex with Su(fu).
Ci is phosphorylated by 3 protein kinases which leads to cleavage of Ci.

Question 12

What are the 3 protein kinases which phosphorylate Ci in Hedgehog signalling?

Answer 12

Protein kinase A, glycogen synthase kinase and casein kinase 1.

Question 13

What happens when Ci is cleaved in the absence of Hedgehog?

Answer 13

Formation of truncated protein CiRep. This enters the nucleus and represses the Hedgehog target gene.

Question 14

What happens when Hedgehog is present?

Answer 14

Binds to patched protein which does NOT inhibit smoothened and inhibits production of CiRep.
Smoothened is phosphorylated by PKA and CK1.
Ci is released from complexes and enters the nucleus to activate it.

Question 15

What happens in the absence of Wnt?

Answer 15

Protein complexes formed which lead to the degradation of beta catenin.
Co receptors bind to TCF transcription factors and prevent expression of certain genes.

Question 16

What happens when Wnt is present?

Answer 16

Wnt binds to Frizzled which allows a signal to be transmitted activating Frizzled and LRP.
Dishevelled and axin are recruited to these.
No destruction complex is formed and beta catenin can accumulate.
Binds to TCF and it enables target gene expression.

Question 17

What are the non-canonical Wnt signalling pathways?

Answer 17

The planar cell polarity pathway and the calcium pathway.

Question 18

What happens during the planar cell polarity pathway?

Answer 18

An activation of RhoGTPase, which activates proteins which moderate cytoskeleton proteins and affect polarity of cells.

Question 19

What happens during the calcium pathway?

Answer 19

Control molecules allow the release of calcium which affects transcription/ cell movement/cytoskeleton.

Question 20

How is the Wnt pathway modulated?

Answer 20

sFRP which can bind to frizzles as well as binding to Wnt, DK1 which binds to co receptor and cannot recruit LRP and Wnf-1.

Question 21

What are the classes of EPH receptors?

Answer 21

Type A, ligands attached to membrane by lipid modification and type B, ligands are transmembrane proteins.

Question 22

What is the exception of receptor which can bind to both ligands?

Answer 22

EPAIA4.

Question 23

What is the role of EPH signalling?

Answer 23

Involved in cellular responses and controls actin cytoskeleton dynamics.

Question 24

What is the relationship between Notch and Delta?

Answer 24

Active Notch represses Delta.

Question 25

Are the levels of Delta identical?

Answer 25

They are not, a small difference in level is amplified.

Question 26

How is Notch activated?

Answer 26

When inactive Notch, CSL is complexed with a repressor protein to prevent target gene expression. Notch is activated by a ligand which allows extracellular domain to be cleaved and intracellular domain to be released and translocated. Domain translocated to nucleus and binds CSL which allows repressor to be released.

Question 27

What is the mastermind co-activator?

Answer 27

It is a co-activator which is recruited and binds to complex in nucleus to allow target gene to be expressed.