Single pass receptors

Question 1

What type of ligand do all single pass receptors respond to?

Answer 1

Peptide ligands

Question 2

What are the three types of single pass receptors (we study)

Answer 2

TGFb receptor
Guanylate cyclase receptors (intrinsic enzyme)
Receptor tyrosine kinases

Question 3

What is an example of a membrane bound guanylate cyclase receptor?

Answer 3

Atrial naturetic peptide receptor

Question 4

What is the ligand for ANF receptor?

Answer 4

Atrial naturetic peptide - released by heart muscle cells

Question 5

What is the response to ligand binding ANF receptor?

Answer 5

Decreases blood pressure - vascular smooth muscle cells bind ANP and relax, kidneys excrete more water and sodium, = decreased venous return to heart

Question 6

ANP binding ANF causes what conformational change?

Answer 6

receptor dimerises, intrinsic guanylate cyclase activity

Question 7

What are cytokines?

Answer 7

small secreted peptide signals, all closely related with 4 conserved helices

Question 8

What are interferons?

Answer 8

Cytokines which make cells more resistant to viral infection

Question 9

What are interleukins?

Answer 9

Cytokines which are important for T cell activation

Question 10

What are Erythopoetins?

Answer 10

Cytokines which increase red blood cell production. They are secreted in the kidneys as precursors, in response to decrease blood oxygen levels.

Question 11

What signaling pathway is activated by cytokine receptor binding?

Answer 11

JAK STAT pathway

Question 12

What is the first response to cytokine binding a receptor?

Answer 12

2 identical transmembrane monomers come together (the monomers are already in a stable complex)

Question 13

Describe JAK STAT pathway

Answer 13

Dimerization of receptors (from binding of cytokine) brings together two associated kinase domains (JAKS)
JAKS crossphosphorylate
This activates the kinases and they phosphorylate the intracellular part of the receptor
SH2 domain on STAT (transcription factor) recognises p-tyr on receptor and binds.
JAK phosphorylates STAT and it dissociates
2 phosphorylated STAT molecules recognise eachothers P-tyr and dimerize
dimerised molecule has intact NLS and translocates to nucleus
Dimer binds DNA tightly and is good transcription facor.

Question 14

How is JAK STAT signalling turned off?

Answer 14

Phosphatase with SH2 domain recognises phosphorylated receptor and dephosphorylates
SOC with SH2 domain binds receptor and ubiquitinates

Question 15

What type of molecule(s) are transforming growth factor beta?

Answer 15

Peptides released by proteolysis (act as dimers)

Question 16

What is an example of a TGFbeta?

Answer 16

bone morphogen protein (paracrine signalling)

Question 17

What type of receptor binds TGFbeta?

Answer 17

Heterodimeric receptor with intracellular kinase activity

Question 18

What occurs after binding of TGFbeta to receptor?

Answer 18

Receptor dimerises, type 2 receptor phosphorylates type 1 receptor.
Type 1 receptor phosphorylates the substrate (TF) SMAD

Question 19

How is SMAD activated?

Answer 19

SMAD2 is autoinhibited. Phosphorylation causes conformational change = activated. Binds second SMAD = SMAD4.
This exposes the NLS.

Question 20

What is usually the response to TGFb signaling?

Answer 20

To inhibit cell proliferation.

Question 21

How is TGFb signaling turned off?

Answer 21

Gene product who’s expression is activated by SMAD3/4 complex = SMURF = SMADA ubiquitination complex.
Also phosphatase which deactivates SMAD

Question 22

How does the TGFbR being in the membrane assist in molecular level of signaling?

Answer 22

2D search in membrane is much faster than 3D search in the cytosol, Protein interaction occurs by random walk