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Immunology PY2 > Lecture 18: Cytokine & Chemokine Receptor Signalling > Flashcards

Lecture 18: Cytokine & Chemokine Receptor Signalling Flashcards

1
Q

the cytokine ____ is responsible for transmitting a signal into the cell upon binding the ligand

A

t

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2
Q

cytokine receptor signalling is achieved by _____ of proteins in the cytoplasm, which results in a rapid pattern of _____ in multiple proteins

A

phosphorylation; alterations

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3
Q

which 2 classes of cytokine recptors lack intrinsic tyrosine kinase domains?

A

class 1 and 2

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4
Q

what are the 2 types of protein kinases?

A

tyrosine and serine/threonine

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5
Q

which inactive protein tyrosine kinase is associated with the alpha chain of class 1 and 2 cytokine receptors?

A

Janus kinase (JAK)

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6
Q

t/f the JAK is present on the alpha chain of class 1 and 2 even when there is no ligand present

A

t

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7
Q

in the absence of _____, the JAK lacks protein tyrosine kinase activity

A

cytokine

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8
Q

cytokine binding to class 1 or 2 receptors induced the association of ______ and activation of _____

A

the 2 separate cytokine receptor subunits; JAKs

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9
Q

activated JAKs in class 1 & 2 create ____ sites where _____ and ____ transcription factors can bind

A

docking; signal transducers and activators of transcription (STAT)

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10
Q

how do the activated JAKs create a docking site for STAT?

A

by phosphorylation of specific tyrosine residues on teh receptors

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11
Q

what domain of STAT bind to the docking site on JAK?

A

SH2

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12
Q

what does the JAK do with the docked STAT?

A

phosphorylates it

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13
Q

after STAT have been phosphorylated by JAK, what happens to them?

A

they translocate to the nucleus as dimers to initiate transcription of specific genes

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14
Q

in the JAK/STAT pathway of class 1 & 2, what determines which genes are transcribed?

A

determined by which specific DNA sequences the STATS bind to in the promotor region of the gene

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15
Q

what adds specificity to the JAK/STAT pathway?

A

there are multiple JAKs and STATs acting in different permutations

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16
Q

the cell cytokine cross-regulation can be explained at the level of _____

A

intracellular signalling

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17
Q

the expression of transcription factor T-Bet drives the cell to ____ differentiation and suppresses the differentiation to ____ cells

A

TH1; TH2

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18
Q

expression of transcription factor GATA-3 promotes differentiation to ___ cells, but inhibits the differentiation to ____ cells

A

TH2; TH1

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19
Q

how can STAT heterodimerization be accomplished?

A

by simultaneous activation of different cytokine receptors that result in phosphorylation of different STATs

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20
Q

IL-6 results in what type of STAT?

A

STAT3

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21
Q

IFN-gamma results in what type of STAT?

A

STAT 1

22
Q

when both IL-6 and IFN-gamma bind to receptors on the same cell, what STAT heterodimers can result?

A

STAT1/STAT3

23
Q

the specificity of cytokine effect is due to what 3 factors?

A
  1. the particular JAK/STAT pathway
  2. STAT specific sequences in the promoter regions of genes
  3. fact that only certain genes can be activated in a particular cell type
24
Q

t/f in any give cell type, only a subset of the potential target genes of a particular STAT may be permitted to be expressed

A

t

25
Q

do chemokines signal the same mechanism as class 1 and 2?

A

no

26
Q

chemokine receptors are coupled with ____ G proteins

A

large heterotrimeric

27
Q

in chemokine receptor signalling, the signal transduction generates second messenger such as _____, _____, _____, ultimately inducing ____ and ____

A

Ras (MAPK), Rho, PLCBeta; AP-1 & NF-kappaB

28
Q

it is now believed that chemokine receptors may be able to signal through JAK, including through ___ and ____, which seems contingent on the ____ of the receptors

A

PKC and JAK-STAT; dimerization (can be hetero or homo)

29
Q

IL-1, TNK and IL-17 signal through a mechanism which involves _____ of multiple different proteins ultimately leading to activation of _____

A

phosphorylation; NF-kappaB

30
Q

what is NF-kappaB?

A

nuclear factor kappa B, a heterodimer s

31
Q

NF-kappaB is sequestered in the cytoplasm by _____

A

IkappaB

32
Q

IkappaBalpha becomes phosphorylated by ____ and then becomes ubiquitinated, which targets it for ___

A

IKK (I kappaB kinase); destruction by the proteosome

33
Q

liberated NFkappaB is free to translocate to the ____ where it has what function?

A

nucleus; directs transcription

34
Q

the range of genes activated by NF-kappaB is wide and includes _____ and ______

A

cytokines/other mediators and adhesion molecules

35
Q

NFkappaB signalling makes its own inhibitor, ____ which serves to stop signalling

A

IkappaBalpha

36
Q

The IL1R1 receptors has an accessory peptide (____) which provides a signal after IL-1 binds

A

IL-1RAcP

37
Q

what is the function of IL-1Ra?

A

blocks IL-1 from binding to the receptor

38
Q

what is IL-1R2 and its role in IL-1 signalling?

A

it is a different polypeptide that is able to bind the IL-1R, but when IL-1 binds, it wont transmit a signal

39
Q

the IL-1R2 receptor can circulate in the blood to prevent ____

A

IL-1 from binding to the actual IL-1 recptor (further inhibits IL-1 signalling)

40
Q

kinases put ___ groups on other molecules

A

phosphate

41
Q

STATs are _____ (direct vs indirect) transcription factors

A

direct

42
Q

if the tyrosine is mutated, will the cytokine receptor still work?

A

no

43
Q

what STAT drives the transcription of T-Bet?

A

STAT 4

44
Q

IL-__ causes production of STAT__, which promotes the actions of what transcription factor?

A

4; 6; GATA3

45
Q

whichever cytokine comes first (___ or ___) determines if the cell will be Th1 or Th2

A

IL-12 or IL-4

46
Q

G proteins of chemokine receptors can signal to ___, which signals to NF-kappaB

A

phospholipase c

47
Q

NFkB is known as the master regulator of _____ bc of the number of cells it acts on as a transcription regulator

A

inflammation

48
Q

how does IkappaB inhibit the actions of NFkB?

A

prevents it from crossing the nucleus

49
Q

what are MAP kinases?

A

signalling molecules that integrate stress signals to your cell

50
Q

give an example of a MAP kinase derived from growth factors

A

ERK1/2

51
Q

give an example of a MAP kinase derived from environmental stress

A

JNK1-3

52
Q

give an example of a MAP kinase derived from inflammatory cytokines

A

p-38a-o

Immunology PY2 (20 decks)

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