Signalling by Cytokines Flashcards
(46 cards)
What do cytokines do and help with?
- Proliferation, differentiation, and function of the immune system.
- Differentiation of cells in the blood forming system.
- Inflammation, including acute phase response.
- Antiviral responses.
What five components do the cytokines include?
- Interleukins.
- Interferons.
- Erythropoietin and Thrombopoietin
- Growth Hormone and Prolactin.
- Leptin.
What are interleukins?
A cytokine, that signals between leukocytes, especially in the immune response and uses the cytokine pathway.
What are interferons?
First discovered for antiviral properties.
What does erythropoietin and thrombopoietin do?
Promote development of RBC (EPO) and platelets (TPO).
What is leptin?
The obesity hormone.
What are the two components of cytokine type receptors?
The membrane bound component and the associated tyrosine protein kinase.
What is the membrane bound component of cytokine receptors?
Has extracellular, cytoplasmic domains and a single transmembrane. May consist of multiple polypeptides depending on the ligand.
What is the associated tyrosine protein kinase (TPK)?
This is a SEPARATE polypeptide, but bound tightly to the cytoplasmic domain of the receptor.
What are the four cytokine-linked TPKs?
- JAK1
- JAK2
- JAK3
- TPK2
What are the three chains that make up the cytokine?
a, B, gamma.
What does the alpha chain do?
The alpha chain forms most of the ligand-binding site, and is unique to that receptor.
What do the beta and gamma chains do?
They are found in more than one cytokine receptor, and are called common chains.
Where do all three chains exist?
All three chains span the membrane with a single TM domain.
What type of receptors are the cytokine receptors?
Type 1, meaning there is WSXWS motif in the extracellular domain where Type 2 lacks this.
What do the cytoplasmic domain chains hold?
A box 1 motif, including a consensus sequence of that box that is needed for interaction with the JAK receptor. Different receptor chains will bind different JAKs.
How does the mechanism of the cytokine receptors work?
Exactly like the growth factor receptors.
- Cytokine receptor dimerizes when ligand is bound to it.
- This brings two JAKs together on the cytoplasmic side.
- The JAKs phosphorylate each other on key Tyr residues.
- In turn, autophosphorylation becomes activated.
- The pTyr residues created on JAK now act as binding sites for the SH2 domains.
What is one key difference between the cytokine receptors and growth factor receptors?
The TPK activity in cytokine receptor signalling is in a SEPARATE but associated polypeptide.
Now that the pTyr residues on JAK as created binding sites, what binds do this site?
Cytoplasmic proteins called STAT proteins that can bind using SH2 domains.
What does STAT stand for?
Signal transduction and activator transcription.
What is STAT made up of?
A DNA binding domain, an SH2 domain, and a conserved Tyr residue near the C terminus.
How do STAT proteins ultimately get into the nucleus and activate transcription of target genes? (6 Steps.)
- Once the SH2 of a STAT protein binds to the pTyr of the JAK, the JAK phosphorylates the STAT on the conserved Tyr near the C-terminus.
- Now each STAT has both a pTyr and an SH2 domain.
- IF these two items are present, two STAT monomers can dimerize.
- These dimers are seen and can then move into the nucleus.
- In some cases, extra protein factors must also bind first.
- In the nucleus, the STAT dimer is recognized and can bind to specific DNA sequences in order to activate transcription of certain target genes.
Define a homodimer?
Two STAT1 monomers: 2 of the same proteins.
Define a heterodimer?
A STAT1 and STAT2 dimerization: 2 different proteins.
