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Cellular Communication > Cytokine receptors and cytokine signalling > Flashcards

Cytokine receptors and cytokine signalling Flashcards

1
Q

What is a cytokine?

A

Any class of immunoregulatory proteins that are secreted by cells especially of the immune system

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2
Q

What do cytokines do?

A

Modulate the behaviour of cells

Physiological events such as hematopoiesis, immunity and inflammation

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3
Q

What are the four major categories of cytokines?

A

TNF family, chemokine family, interferon family, interleukin family

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4
Q

What is the function of interferons?

A

Anti-viral activity

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5
Q

What is the function of TNFs (Tumour Necrosis Factor)

A

A pro-inflammatory cytokine

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6
Q

What is the function of chemokines?

A

Control and direct cell migration

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7
Q

What is the function of interleukins?

A

They have various functions

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8
Q

What type of receptors are the majority of cytokines?

A

Kinase-linked receptors

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9
Q

True or false?

Unlike other kinase-linked receptors, cytokine receptors dont possess intrinsic catalytic activity

A

True

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10
Q

What class of cytokine receptors comprise the majority of kinase-linked cytokine receptors?

A

Class 1 and 2

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11
Q

What region forms the basis of all cytokine receptor structures?

A

The cytokine homology region (CHR)

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12
Q

Where does cytokine binding occur and what does it lead to?

A

In the dimerization/oligomerization of receptors which leads to the juxtapositioning of JAKs.

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13
Q

Where do JAKs phosphorylate cytokine subunits?

A

Conserved tyrosine sites

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14
Q

What can occur on phosphorylated receptor sites?

A

Docking sites that permits binding or STAT transcription factors

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15
Q

Once phosphorylated, STAT proteins change conformation and form high affinity homo/hetero-dimers via the interaction of what?

A

Interaction of SH2 domain of one STAT molecule with the tyrosine phosphorylated residue of another

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16
Q

How are the dimerized STATs able to translocate into the nucleus and regulate gene expression?

A

Through the binding to TTC(N)2-4GAA consensus DNA binding elements in STAT-target genes

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17
Q

What is the function of the STA-regulated genes, SOCS proteins?

A

They negatively feedback on the JAK-STAT signalling pathway to terminate cytokine receptor signalling (Inhibitors of cytokine receptor signalling)

18
Q

What are the eight known family members of SOCS?

A

SOCS1-SOCS7 and CIS

19
Q

What is an example of a cytokine receptor that is produced by antigen-activated T cells?

A

Interleukin-2 receptor (IL-2R)

20
Q

What type of affinity and signal do Naiive T cells have?

A

Intermediate affinity complex

Weak signal

21
Q

What type of affinity and signal do Activated T cells have?

A

High affinity complex

Strong signal

22
Q

Describe the 3 step pathway of the IL-2 receptor

A

1) IL-2 receptor activates several intracellular signal transduction pathways
2) JAK1/3 -> STAT5 pathway
3) Cell cycle entry and proliferation of activated T cells

23
Q

Explain the link of IL-2 and the STAT activated

A

IL-2 activates more STAT5 than STAT3 and more STAT3 than STAT1

24
Q

What does IL-2R/JAK/STAT5 all have in common with each other?

A

Controls Myc and cyclin D expression in activated T cells which leads to T cell growth and cell cycle entry

25
Q

What is JAK1/3 inhibition effective in doing?

A

Effective at amerliorating cytokine-induced disease in vivo

26
Q

What is the function of Granulocyte-macrophage colony-stimulating factor receptor (GM-CSFR)

A

A multifunctional cytokine that regulates inflammatory responses, including emergency responses in the bone marrow

27
Q

What is recombinant GM-CSF clinically used for?

A

To accelerate white blood cell recovery following autologous bone marrow transplantation

28
Q

What does GM-CSF signal via?

A

Via a multimeric cytokine receptor complex that contains a shared receptor subunit, the common beta chain

29
Q

What two subunits is GM-CSF composed of?

A

heterodimer composed of an alpha subunit (GMRa) and beta c subunit

30
Q

What is the beta c subunit also involved in?

A

Signal transduction through its interaction with JAK2

31
Q

What are the cytoplasmic domains of both GMRa and Bc essential for?

A

Receptor activation

32
Q

What does the low-affinity receptor complex consist of?

A

GM-CSF bound to GMRa

33
Q

What forms the high-affinity hexameric receptor complex?

A

Interaction of GM-CSF/GMRa with free (dimeric) Bc subunits

34
Q

How are dodecamer (or higher-order) receptor complexes formed?

A

Form by lateral aggregation of hexameter complexes in the plasma membrane to form a fully competent signalling complex

35
Q

What is able to dimerize and transphosphorylate within the dodecamer complex but not within the hexamer complex?

A

JAK2 associated with Bc (common beta chain) subunits

36
Q

What does GM-CSF signal via?

A

Via a classical JAK2-STAT5 signalling pathway

37
Q

What is hematopoiesis?

A

Formation of red blood cells in the bone marrow

38
Q

What does JAK stand for and what are they?

A

Janus kinases

Family of intracellular tyrosine kinases

39
Q

What does STAT stand for and how many family members?

A

Signal Transducers and Activators of Transcription

7 family members

40
Q

How does an unphosphorylated STAT exist?

A

Antiparallel dimer in the cytoplasm where SH2 domains are far apart from each other

41
Q

How does STAT exist when the JAK phosphorylates the tyrosine residue?

A

Induces a large rotation in the two subunits of the dimer and allows SH2 domains to come within close proximity of eachother
Now competent to binding with DNA

Cellular Communication (7 decks)

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