receptors and signal transduction Flashcards
(76 cards)
1
Q
what substances bind to GCPRs
A
chemokines and prostaglandins
2
Q
what substances bind to RTKs (or Src kinases)
A
insulin (RTK)
integrin (Src)
3
Q
nuclear receptors are _______ receptors and can ben nuclear or
A
intracellular
translocate to nucleus after binding
4
Q
lipid soluble ligands bind to _______ receptors
A
nuclear
(glucocorticoids/Vit D/homrones)
5
Q
signal transduction signaling requires a ligand-induced
A
clustering or receptors (called cross-linking)
6
Q
clustering and conformational alterations result in changes in the _______ portion of the receptor that promotes interactions with other signaling molecules
A
cytosolic
7
Q
in the nuclear phase of signal transduction, modified ________ ________ enter the nucleus and induce the expression of target genes that have a binding site in the promoter
A
transcription factors
8
Q
the enzymatic phosphorylation of tyrosine, serine, or threonine in the cytosolic portion of the receptor initates the
A
signal transduction
9
Q
the covalent addition of ubiquitin molecules either target proteins for ________ or drive _______ _______ in many cells
A
degradation
signal transduction
10
Q
protein signaling molecules can also be modifed by the covalent addition of _______ that may promote plasma membrane _______ of signaling molecules
A
lipids
localization
11
Q
The N-terminal tails of histones can undergo _______ and _______ that modulate: gene expression, DNA replication, and DNA recombination
A
acetylation and methylation
12
Q
moduar signaling proteins contain ______ and ______ domains
A
kinase and binding
13
Q
all modular proteins are made of _____ , _____ , and ______ domains, or some combo of them
A
SH2, SH3, and PH
14
Q
SH2 domains bind
A
phosphotyrosine
15
Q
SH3 domains bind
A
proline rich peptides
16
Q
PH domains bind
A
inositol phospholipids
17
Q
modular signaling proteins - tyrosine kinase families:
1.
2.
3.
A
- Src
- Syk
- Tec
18
Q
Src:
examples:
domains:
A
examples: lyn, fyn, lyk
domains: SH2, SH3
19
Q
Syk:
- examples
- domains:
A
- examples: syk and Zap-70
- domains: SH2 (x2)
20
Q
Tec:
- examples:
- domains:
A
- examples: Btk and Itk
- SH2, SH3, and PH
21
Q
adaptor proteins are considered the ______ of the signaling complex and do not have ______ activity
A
scaffolding
catalytic
22
Q
main job of adaptor proteins
A
link enzymes and promote assembly of signaling complex
23
Q
main adaptor proteins
A
LAT (linker for T-cell activation) = adaptor for T-cell signaling
BLNK (B-cell linker) = adaptor for B-cell signaling
GADS
SLP-76
VAV
24
Q
no LAT =
A
no mature T cells
25
_LAT adaptor protein:_
is the only ______ membrane protein
after phosphorylation, LAT recruits
integral
PLC-gamma and GADS
26
_SLP-76 adaptor protein:_
is _____ rich
binds to _____ domain on GADS → phosphorylation of ______ residue
is proline rich
binds to SH3 domain on GADS → phosphorylation of tyrosoine residue
27
_VAV adaptor protein:_
is a \_\_\_\_\_
activate _____ \_\_\_\_\_ rearrangements and _____ changes
GEF
actin cytoskeletal ; and transcriptional
28
ITAMs =
ITAMs are found on _____ and \_\_\_\_\_
ACTIVATE
CD3 and zeta chains
29
TCR complex consists of
the alpha-beta TCR non-covalently linked to the CD3 and zeta proteins
30
each CD3 protein has ______ ITAMs
2
31
each zeta protein has _____ ITAMs
6
32
the number of ITAMs activated signals the
affinity of the Ag to the TCR
33
weak TCR signal for self Ag = ____ selection
positive
34
strong TCR signal for self Ag = ____ selection
negative
35
the longer an Ag is bound to TCR, _______ number of active ITAMs
increased
36
ITIMs =
INHIBIT
37
ITIMs are commonly found on
FcgammaRIIB (found on B cells and myeloid cells)
38
CD8 coreceptors interact with MHC \_\_\_\_\_\_
CD4 coreceptors interact with MHC \_\_\_\_\_\_
class I
class II
39
CD4 coreceptor has 4 ______ - like domains
Ig
40
CD8 coreceptors have a ____ and ____ domain, each with 1 _____ - like chain
alpha and beta domain,
Ig-like chain
41
CD8 binds to class I MHC molecules and interacts with
beta2 microglobulin
42
the immunologic synapse is initiated by TCR recognition of
peptide-MHC complex
43
_immunological synapse_
T cell accessory molecule: Fxn: Ligand: location
1. CD3 : signal transduction : none
2. zeta : signal transduction : none
3. CD4 : signal transduction : MHC- II - APC
4. CD8 : signal transduction : MHC-I - all nucleated
5. CD28 (CD80/86) : signal trans-costim : B7-1/B7-2 -APC
6. CTLA-4 : signal transduction : B7-1/B7-2 - APC
7. PD-1 : signal trans : PD-L1/PD-L2 - APC, tissue/tumor cells
8. LFA-1 : adhesion : ICAM-1 : APC, endothelium
9. CD2 : ----------- : LFA-3
44
TCRs of circulating CD4 T cells that recognize pMHC II form a _____ bond that is stabilized by _____ molecule via noncovalent interaction with the portion of MHC II that is not involved in _____ binding
weak
CD4
peptide
45
the LFA-1:ICAM-1 complexes move ______ from the pMHC:TCR:CD4 complex forming the peripheral circle of molecules involved in the immunological synapse
away
46
CD2:LFA-3 complexes and costimulatory CD28:CD80/86 move ______ the pMHC:TCR:CD4 complex
toward
47
formation of the pMHC:TCR:CD4 comlpex provides a ______ signal
the first signal is necessary but not sufficient to stimulate:
a second signal provided by costimulatory molecules is required for:
first
a naive T cell to proliferate and differentiate
T cell activation
48
upon Ag recognition, the ITAMs are ________ and dock other signaling molecules
phosphorylated
49
TCR-Dependent Cascade
1. TCR engages pMHC II
2. CD4 engages pMHC II to activate Lck
3. Lck phosphorylates ITAMs to activate ZAP-70
1. ZAP-70 Pathway 1
1. ZAP-70 phosphorylates LAT and activates PLC-gamma
2. PLC-gamma cleaves PIP2 to form DAG and IP3
3. DAG + Ca2+ activates PKC
1. PKC phosphorylates IkBeta to migrate to the nucleus
4. IP3 + Ca2+ activates calcineurin
1. calcineurin activates NFAT
2. ZAP-70 Pathway 2
1. ZAP-70 phosphorylates LAT
2. LAT activates ras and rac
3. ras and rac initiate phosphyrlation cascades to activate AP-1 family transcriptional factors
\*ZAP-70 autophosphorylates after interaction with active zeta chains
\*AP-1 also called Jun??
50
what activates NFKB pathway
1.
2.
3.
1. TCR/BCR
2. TLRs
3. CD40
51
NFKB pathway
PKC phosphorylates and activates IKBeta → phosphorylated IKBeta is ubiquitinated and sent to proteasome → this frees NFKB to go to nuclues and promote IL-2 transcription
52
NFAT pathway
calcineurin activates NFAT (by dephosphorylating?) → NFAT migrates to nucleus to promote IL-2 transcription
53
clonal anergy is the term that describes T cell ________ at the cellular level
unresponsiveness
54
hyporesponsive state of T cell is characterized by a reduced capacity to synthesize
IL-2
55
anergic T cells do not _______ in response to appropriate Ag stimulation
proliferation
56
_Co-stimulation: T cell activation:_
\_\_\_\_\_ (on T-cells) → _____ (on APCs)
\_\_\_\_\_ (on T-cells) → _____ (on APCs)
CD28 (on T-cells) → CD80/80 (also B7) (on APCs)
CD40L (on T-cells) → CD40 (on APCs)
57
_Co-Stimulation: T cell inhibition_
\_\_\_\_\_ (on T-cells) → _____ (on APCs)
\_\_\_\_\_ (on T-cells) → _____ (on APCs)
CTLA-4 (on T-cells) → CD80/86 (on APCs)
PD-1 (on T-cells) → PDL1 (on APCs)
58
_anergy can be induced by substimulatory levels of Ags in the absence of:_
\_\_\_\_\_\_ interactions beween costimulatory receptors on T cells and counter-receptors on APCs
a costimulatory signal provided by soluble \_\_\_\_\_\_
CD28:CD8086
cytokines
59
anergy can be overcome by
exogenous IL-2
60
if only first T cell signal is present (TCR:pMHC:CD4) , only ______ is produced which leads to decreased transcription of \_\_\_\_\_\_
NFAT
IL-2
61
NFAT activation alone =
anergy
62
naive B mature B cells express
IgM and IgD on their surface
63
class-switched and memory B cells expess either
IgM, IgG, IgA, or IgE
64
transmembrane signlaing componeent of BCR
Ig-alpha and Ig-beta
65
Ig-alpha and Ig-beta contain ______ in their cytoplasmic tails
ITAMs
66
_B cell co-receptors:_
1.
2.
3.
4.
5.
1. CD19 functions as the dominant signaling component
2. CD21 is also known as a complement receptor 2 (CR2) and helps to lower the activation threshold
3. CD32 is also known as Fcgamma receptor type IIb (FCgammaRIIB) - inhibitory and contains ITIMs
4. CD81 stabilizses CD 19
5. CD22 is inhibitory and B cell specific (lacking can cause autoimmunity)
67
BCR signaling cascade
1. BCR engages epitope (signal 1)
2. Costimulatory molecules bind (signal 2) which activates lyn, lck, blk, fyn which then phosphorylate ITAMs on Ig-alpha and Ig-beta to activate Syk
3. Syk phosphorylates and activates PLC-gamma
4. PLC-gamma cleavew PIP2 to form DAG and IP3
1. DAG activates PKC
1. PKC phosphoyrlates IkB (releasing NFkB)
1. NFkB migrates to the nucleus to promote transcription of IL-2
2. IP3 + Ca2+ activates calcineurin
1. calcineurin activates NFAT
1. NFAT migrates to nucleus to promote transcription of IL-2
68
_BCR signaling:_
activation = _______ of ITAMs and ______ of ITIMs
deactivation = _______ of ITAMs and _______ of ITIMs
phosphorylation dephosphorylation
dephosphorylation phosphorylation
69
B cell signaling is initiated by Ab binding and ______ of BCR receptors
crosslinking
70
_complement and CR2 activation of BCR:_
1. C3b on bacteria cleaved into _____ by factor I
2. C3d bind to ______ receptor on B cell as Ag binding to the BCR
3. C3d:CR2 binding brings ______ close to the BCR associated kinases; CD19 has to be stabilized with \_\_\_\_\_\_
4. CD19 _____ are pohphorylated, allowing recruitment of Lyn and PI3-kinase
5. overall effect:
1. C3d
2. CR2 (CD21)
3. CD19 CD81
4. ITAMs
5. greatly enhanced signaling
71
the CR2:CD19:CD81 complex is often called the B cell coreceptor complex because CR2 binds to Ags through attached ______ at the same time that BCR binds directly to the Ag
C3d
72
B cell activation is tightly controlled to limit immune resopnses against microbes in order to avoid ______ \_\_\_\_\_\_\_ to host tissues
collateral damage
73
inhibitory receptors typically recruit and activate _______ that counter signaling events induced by Ag receptors
phosphatases
74
_BCR inhibitory signaling:_
1. binding of the inhibitory signal → phosphorylation ofITIMs by ______ family
2. phosphorylated ITIMs recruit ______ domain phosphatases (SHP and SHIP)
3. SHP and SHIP removes phosphates groups from \_\_\_\_\_\_
(Example:)
1. Src
2. SH2
3. ITAMs (PIP3)
(Example: binding via the CD32 (FcgammaRIIB) and CD22
75
inhibitory signaling in lymphocytes is mediated primarily by inhibitory receptors and also by
E3 ubiquitin ligases
76
_B-cell and T-cell interaction (most B cell responses require CD4 T cell help):_
1. ______ on B cell will present Ag to T cell ______ complex
2. CD28:CD80/86 provides costimulation for release of \_\_\_\_
3. T cell will induce expression of _____ to bind to _____ on B cell
4. B cell upregulates _____ and increases the signaling cascade leading to activation
1. MHC II TCR:CD3:CD4
2. IL-4
3. CD40L CD40
4. IL-4R
