Lecture 8 (Exam 2) Flashcards
(106 cards)
1
Q
These are generally integral transmembrane proteins present on the plasma membrane.
A
Receptors
2
Q
The extracellular domains recognize soluble _______ or membrane structures of neighboring cells.
A
Ligands
3
Q
Ligand-binding involves a _________ alteration of the receptor.
A
Conformational
4
Q
Signaling requires a ligand-induced clustering of receptors, called…
A
Cross-linking
5
Q
Clustering and conformational alterations result in changes in the cytosolic portion of the receptor that promotes interactions with other ________ molecules.
A
Signaling
6
Q
________ receptors are intracellular transcription factors that are activated by lipid-soluble ligands (for example, estrogen, progesterone, retinoic acid, etc.) that can cross the plasma membrane.
A
Nuclear
7
Q
The enzymatic phosphorylation of ______, ______, or ______ in the cytosolic portion of the receptor initiates the signal transduction.
A
Tyrosine
Serine
Threonine
8
Q
These enzymes are called _______ kinases:
- Tyrosine kinases phosphorylate specific tyrosine residues
- Serine/threonine kinases phosphorylate serine or threonine residues
- Lipid kinases phosphorylate lipid substrates
A
Protein
9
Q
There are also specific ________ for all types of protein kinases which remove the phosphate residue and thus modulate signaling.
A
Phosphatases
10
Q
Phosphatases usually play (EXCITATORY/INHIBITORY) roles in signal transduction.
A
Inhibitory
11
Q
Another protein modification that can facilitate a signaling event is the covalent addition of ________ molecules that either target proteins for degradation or drive signal transduction in many cells.
A
Ubiquitin
12
Q
Protein signaling molecules can also me modified by the covalent addition of ______ that may promote plasma membrane localization of signaling molecules.
A
Lipids
13
Q
Another protein modification that can facilitate signaling events are the ________ and ________ of the N-terminal tails of histones. This effects gene expression, DNA replication, and DNA recombination.
A
Acetylation
Methylation
14
Q
The components of signaling pathways can either be ________ signaling proteins or ________ proteins.
A
Modular
Signaling
15
Q
Many eukaryotic signal transduction proteins have component-based architectures. They are built from combinations of (1) _________ domains and (2) _________ domain(s).
A
Interaction
Catalytic
16
Q
In the modular architecture of signaling proteins, intact these proteins display the sophisticated _________ regulation – the alteration of the activity of a protein through the binding of an effector molecule at a specific site.
A
Allosteric
17
Q
In the modular architecture of signaling proteins, the protein’s output activity is tightly (REPRESSED/ACTIVATED) under basal conditions. However, it can be robustly (REPRESSED/ACTIVATED) by a specific set of input effector ligands.
A
Repressed
Activated
18
Q
Tyrosine kinase families are key players in the regulation of the immune functions. These families include…
A
Src family
Syk family
Tec family
19
Q
Signaling molecules are composed of distinct domains, each with a specific binding or _______ function.
A
Catalytic
20
Q
Who are the members of the Src family?
A
c-Src
Lyn
Fyn
Lck
21
Q
Who are the members of the Syk family?
A
Syk
ZAP-70
22
Q
Who are the members of the Tec family?
A
Tec
Btk
Itk
23
Q
_____ domains are composed of about 100 amino acids folded into a particular conformation that bind to phosphotyrosine-containing peptides in certain proteins.
A
SH2
24
Q
SH2 domains (x2) are present in _____ and _____ tyrosine kinases, which bind phosphotyrosine motifs in the Ag receptor complex.
A
Syk
ZAP-70
25
_____ domains are composed of about 50 amino acids folded into a particular conformation that bind to proline-rich stretches in certain proteins.
SH3
26
_____ domains found in the Tec family kinases recognize specific phospholipids.
PH (Pleckstrin Homology)
27
_____ tyrosine kinase recognizes a lipid moiety on the inner leaflet of the plasma membrane termed phosphatidylinositol triphosphate (PIP3).
Btk (Tec family)
28
How many functional domains are there of the Src?
Five
29
This is the 1st domain of Src, it's on the n-terminal and contains a myristic acid moiety, essential for its localization to the inner surface of the cell membrane.
SH4 domain
30
This is the 2nd domain of Src and provide functional specificity to each member of the Src family.
Unique domain
31
This is the 3rd domain of Src, and it binds proline-rich sequences to mediate intra- and intermolecular interactions.
SH3 domain
32
This is the 4th domain of Src, and it binds phosphorylated tyrosine residues on Src and other proteins.
SH2 domain
33
This is the 5th domain of Src, and it is a catalytic domain.
SH1 (kinase) domain
34
Src can be switched from an inactive to an active state by ___________ state.
Phosphorylation
35
There are two major phosphorylation sites on Src, at ______ (or ______) and at ______.
Tyr416 (Y416)
| Tyr527
36
On Src, a more critical phosphorylation site is Tyr527. The phosphorylation of Tyr527 (ACTIVATES/INACTIVATES) Src through the interaction of P-Tyr527 with the SH2 domain, which effectively folds Src up into a closed, inaccessible bundle.
Inactivates
37
Dephosphorylation of Tyr527 opens up the molecule (Src) to an (INACTIVE/ACTIVE) state.
Active
38
A ______ can be auto-phosphorylated, which activates Src by displacing the P-______ from the binding pocket, allowing the substrate to gain access.
Tyr416
| Try416
39
Many of the substrates that Src can phosphorylate with its ________ domain form part of signaling process.
Kinase (SH1)
40
Signaling systems often involve a ________ mechanism of sequential phosphorylation and dephosphorylation of proteins in the ________.
Cascade
| Cascade
41
Adaptor proteins (DO/DO NOT) have a catalytic activity.
Do not
42
Adaptor proteins contain only _______-_______ interaction domains.
Protein-protein
43
Adaptor proteins are molecular hubs that physically link different enzymes and promote the assembly of complexes of signaling molecules. These proteins include...
LAT (Linker for the Activation of T cells)
| BLNK (B cell linker)
44
Adaptor proteins may contain several _____ and _____ domains.
SH2
| SH3
45
Adaptor proteins may contain a few _______ residues that may serve as docking sites for other signaling proteins with SH2 domains.
Tyrosine
46
Adaptor proteins often contain _______-rich stretches that can bind other proteins that contain SH3 domains.
Proline
47
The essential role of LAT (Linker for the Activation of T cells) has been first demonstrated in _______ T-cell line that express no LAT and are defective in TCR-mediated signaling.
Jurkat
48
Jurkat cells transfected with the LAT gene (REDUCE/RESTORE) TCR signaling, indicating that LAT is indispensable for T-cell activation via the TCR.
Restore
49
Targeted disruption of the LAT gene in mice revealed a requirement for LAT in ______ development.
T-cell
50
Animals lacking LAT exhibited an early arrest of thymocyte development and no mature alpha/beta T-cells were found in their _______ _______ organs.
Peripheral lymphoid
51
This is a type of adaptor protein that is an integral membrane protein.
LAT
52
This is a cytosolic adaptor protein belonging to the Grb2 family.
GADS
53
This is an adaptor protein that has proline-rich domain and SH2 binding domains.
SLP-76
54
The ______ proteins are guanine nucleotide exchange factors (GEFs) for GTPases that activate actin cytoskeletal rearrangements and transcriptional alterations.
VAV
55
When LAT is phosphorylated, it recruits ________ and the _______ adaptor protein.
```
Phospholipase C (PLCy)
GADS
```
56
Once LAT is phosphorylated and has recruited PLCy and GADS, then _______ associates with GADS via SH3 domain and recruits ______ after being tyrosine-phosphorylated.
SLP-76
| VAV
57
The TCR complex consists of the ______ ______ non-covalently linked to the _____ and _____ proteins. The association of these proteins with one another is mediated by charged residues in their transmembrane regions.
Alpha/Beta TCR
CD3
Zeta
58
Both Alpha and Beta TCR chains have _______-terminal cytoplasmic tails that are 5 to 12 aa long.
Carboxyl
59
In Alpha and Beta TCR chains, their cytoplasmic regions are too small to transduce signals so _____ and _____ proteins serve as signal-transducing subunits of the TCR complex.
CD3
| Zeta
60
_____ and _____ interact with class I and class II MHC molecules (respectively).
CD8
| CD4
61
CD4 has --
- _____ extracellular Ig-like domains
- A ________ transmembrane region
- A highly _______ cytoplasmic tail 38 amino acids long.
Four
Hydrophobic
Basic
62
CD8 is composed to two related chains called _____ and _____.
CD8a (alpha)
| CD8B (beta)
63
CD8a and CD8B have --
- ______ extracellular Ig domain(s)
- A ________ transmembrane region
- A highly _______ cytoplasmic tail that is about 25 amino acids long.
One
Hydrophobic
Basic
64
CD8 binds to class I MHC molecules that also interact with ____ _________.
B2 microglobulin
65
Activating immune receptors have separate polypeptide chains for recognition and associated signaling polypeptide chains that contain cytosolic ______.
ITAMs (immunoreceptor tyrosine-based activating motifs)
66
Inhibitory immune receptors in the immune system typically have _______ on the cytosolic portion of the same chain that uses its extracellular domain for ligand recognition.
ITIMs (immunoreceptor tyrosine-based inhibitory motifs)
67
The FcyRIIB is an (ACTIVATING/INHIBITORY) receptor found on B cells and myeloid cells. It contains the Fc receptor for IgG.
Inhibitory
68
FcERI is an (ACTIVATING/INHIBITORY) receptor and contains the Fc receptor for IgE.
Activating
69
The TCR complex has _____ signaling chains and _____ ITAMs.
6x
| 10x
70
The number of ITAMs phosphorylated is a cytosolic interpretation of _____ affinity to the TCR. The stronger or prolonged binding of _____ to the TCR results in increasing numbers of phosphorylated ITAMs.
Ag
| Ag
71
Ag affinity of TCR can influence the nature of the cellular response at different stages of differentiation and activation. (WEAK/STRONG) TCR signals are required for positive selection of T cells in the thymus. (WEAK/STRONG) TCR signals in the thymus results in negative selection of T cells and their death by apoptosis.
Weak
| Strong
72
The immunologic synapse stabilizes T cell-APC interaction and promotes the migration of adhesion molecules within the T cell membrane. Cytoplasmic tails of some of these molecules contain _______ that initiate a signaling cascade when brought into close proximity.
ITAMs
73
The cytoplasmic tails of _____ complex molecules bear ITAMs.
CD3
74
The cytoplasmic tails of CD3 complex molecules bear ITAMs. These ITAMs contain four amino acids, indicated as two Xs flanked by ______ and ______. Multiple ITAMs are located at 10-12 amino acid intervals along the cytoplasmic tail. In contrast, the cytoplasmic tails of the TCR lack ITAMs (too short).
Tyrosine (Tyr)
| Lysine (Lys)
75
A series of stimuli activate NF-kB activation in T and B lymphocytes and other immune cells. Activated _____ phosphorylates _____ on 2 conserved serine residues and induces _____ polyubiquitinylation.
IKK
IkB
IkB
76
Ubiquitin induces recognition of IkB-UUUUU by the ________ and causes successive proteolytic degradation.
Proteasome
77
Following the IkB degradation, the cytoplasmic NF-kB dimers are released and translocated into the _______, where gene transcription is activated.
Nucleus
78
Following the IkB degradation, the cytoplasmic NF-kB dimers are released and translocated into the _______, where gene transcription is activated.
Nucleus
79
Put the following steps of the Ras-MAP kinase pathway in order --
A. ZAP-70 phosphorylates/activates membrane-associated adaptor protein LAT.
B. Upon Ag recognition, CD4/CD8-associated Lck is activated.
C. SOS converts Ras-GDP to Ras-GTP that activates MAP kinase and ERK.
D. Lck phosphorylates ITAMs of zeta chains.
E. The cascade activates AP-1.
F. Then, ZAP-70 binds to the phosphorylated zeta chains and become self-phosphorylated and activated.
G. Activated LAT binds GADS adaptor that docks an GTP/GDP exchange factor called SOS.
1. B
2. D
3. F
4. A
5. G
6. C
7. E
80
This is the term that describes T-cell unresponsiveness at the cellular level.
Clonal anergy
81
Clonal anergy is a hyporesponsive state characterized by a reduced capacity to synthesize ______.
IL-2
82
Anergia T-cells (DO/DO NOT) proliferate in response to appropriate Ag stimulation.
Do not
83
Anergy can be broken by exogenous (outside) ______.
IL-2
84
Anergy can be induced by substimulatory levels of Ags in the (ABSENCE/PRESENCE) of --
- CD28:CD80/86 interactions between costimulatory receptors on T-cells and counter-receptors on APCs
- A costimulatory signal provided by soluble cytokines
Absence
85
TCR (signal 1) and CD28 (signal 2) induce different signaling pathways that result in the activation of several transcription factors. In the nucleus, ______ cooperates with AP1 and NF-kB to induce gene expression of a productive immune response.
NFAT
86
When TCR engagement (signal 1) occurs in the absence of CD80/CD28 (signal 2) co-stimulation, calcium-mediated signals induce the activation of ______ only. This alone elicits the expression of a distinct set of anergy-inducing genes.
NFAT
87
Products of anergy-inducing genes inhibit ______ function at different levels and induce a status of ______ unresponsiveness.
T-cell
| T-cell
88
The immunologic synapse is initiated by TCR recognition of ______.
pMHC
89
TCRs of circulating CD4+ T cells that recognize peptide and MHC class II (pMHC class II) form a (STRONG/WEAK) bond that is stabilized by CD4 molecule, aka the non covalent interaction of CD4 with the non peptide-bonding portion of MHC class II.
Weak
90
Adhesion molecules expressed by T-cells (leukocyte function antigen-1, LFA-1) interact with ______ on APC.
ICAM-1 (Intercellular Adhesion Molecule 1)
91
The LFA-1 and ICAM-1 complexes move (TOWARD/AWAY) pMHC, TCR, and CD4 complex.
Away
92
At the same time as LFA-1 and ICAM-1 complexes, _____ and _____ complexes and costimulatory _____ and _____ move toward the pMHC, TCR, and CD4 complex.
CD2
LFA-3
CD28
CD80/86
93
Formation of the pMHC, TCR, and CD4 complex provides a first signal through the TCR-associated ______ complex to the T-cell. The first signal is necessary but NOT SUFFICIENT to stimulate a naive T-cell to proliferate and differentiate.
CD3
94
T/F. A second signal (or more properly, a group of signals) provided by one or more co-stimulatory molecules is also required for T-cell activation.
True
95
The _____ is composed of three polypeptide chains (y, d, and e) arranged in two pairs (ye and de).
CD3
96
The ______ are the regions of signaling proteins that are phosphorylated and dock other signaling molecules.
ITAMs
97
These T-cell accessory molecules function in signal transduction by the TCR complex. They are expressed on the T-cell and contain ITAMs.
CD3
| zeta chains
98
CD4 is a T-cell accessory molecule that functions in signal transduction. It is expressed on the (T-CELL/APC) and its ligand, class II MHC, is expressed on the (T-CELL/APC).
T-cell
| APC
99
CD8 is a T-cell accessory molecule that functions in signal transduction. It is expressed on the (T-CELL/APC) and its ligand, class I MHC, is expressed on the (T-CELL/APC).
T-cell
| APC
100
CD28 is a T-cell accessory molecule that functions in signal transduction (co-stimulation). It is expressed on the (T-CELL/APC) and its ligand, which can be B7-1, B7-2, CD80, or CD86, is expressed on the (T-CELL/APC).
T-cell
| APC
101
CTLA-4 (a homolog CD28) is a T-cell accessory molecule that functions in signal transduction (negative regulation) or T-cell inhibition. It is expressed on the (T-CELL/APC) and its ligand, which can be B7-1, B7-2, CD80, or CD86, is expressed on the (T-CELL/APC).
T-cell
| APC
102
PD-1 (Program death-1) is a T-cell accessory molecule that functions in signal transduction (negative regulation) or T-cell inhibition. It is expressed on the (T-CELL/APC) and its ligand, PD-L1/PD-L2, is expressed on the (T-CELL/APC).
T-cell
| APC (also tissue cells and tumor cells)
103
LFA-1 functions in adhesion for the T-cell. Its ligand is ICAM-1. Which one is on the T-cell and which one is on the APC?
```
LFA-1 = T-cell
ICAM-1 = APC (and endothelium)
```
104
This tyrosine kinase family has both and SH3 and SH2 domain.
Src (Lyn and Lck)
105
This tyrosine kinase family has two SH2 domains.
Syk (Syk and ZAP-70)
106
This tyrosine kinase family has and SH2 domain, an SH3 domain, and a PH domain.
Tec (Btk and Itk)
