Lecture 7: Immune Receptors and Signal Transduction Part I

Question 1

True or False:

Ligand-binding involves a conformational alteration of the receptor.

Answer 1

True

Question 2

What does signaling require?

Answer 2

ligand-induced clustering of receptors, called cross-linking

Question 3

What does clustering and conformational alterations result in?

Answer 3

changes in the cytosolic portion of the receptor that promotes interactions with other signaling molecules

Question 4

What are nuclear receptors?

Answer 4

intracellular transcription factors that are activated by lipid-soluble ligands (estrogen, progesterone, retinoic acid, etc.) that can cross the plasma membrane

Question 5

What do the extracellular domains of receptors recognize?

Answer 5

soluble ligands or membrane structures of neighboring cells

Question 6

What does the phosphorylation of tyrosine, serine, or threonine in the cytosolic portion of the receptor do?

Answer 6

initiates the signal transduction

Question 7

What do lipid kinases do?

Answer 7

phosphorylate lipid substrates

Question 8

What do serine/threonine kinases do?

Answer 8

phsphorylate serine or threonine residues

Question 9

What do tyrosine kinases do?

Answer 9

phosphorylate specific tyrosine residues

Question 10

What do phosphatases do?

Answer 10

remove the phosphate residue and thus modulate signaling

Question 11

What enzyme usually plays inhibitory roles in signal transduction?

Answer 11

phosphatases

Question 12

What does the SH2 domain bind to?

Answer 12

binds phosphotyrosine

Question 13

What does SH3 domain bind to?

Answer 13

binds proline-rich peptides

Question 14

What does PH domain bind to?

Answer 14

binds inositol phospholipids (e.g., PIP3)

Question 15

What are the 3 tyrosine kinase families?

Answer 15

> Src family (c-Src, Lyn, Ryn, and Lck)

> Syk family (Syk and ZAP-70)

> Tec family (Tec, Btk, and Itk)

Question 16

What do SH2 domains (Src Homology 2) present?

Answer 16

Syk and ZAP-70 tyrosine kinases bind phosphotyrosine motifs in the Ag receptor complex.

Question 17

How many amino acids are SH2 domains composed of?

Answer 17

100 amino acids

Question 18

How many amino acids are SH3 domains composed of?

Answer 18

50 amino acids

Question 19

What recognizes PIP3?

Answer 19

Btk tyrosine kinase recognizes a lipid moiety on the inner leaflet of the plasma membrane termed phosphatidylinositol trisphosphate (PIP3).

Question 20

What do adaptor proteins lack?

Answer 20

catalytic activity

Question 21

What are the only domains that adaptor proteins contain?

Answer 21

protein-protein interaction domains

Question 22

What are adaptor proteins?

Answer 22

Molecular hubs that physically link different enzymes and promote the assembly of complexes of signaling molecules:

• LAT (Linker for the Activation of T cells)
• BLNK (B cell linker)

Question 23

Can adaptor proteins contain a few SH2 and SH3 domains?

Answer 23

Yes

Question 24

True or False:

Adaptor proteins often contain proline-rich stretches that can bind other proteins that contain SH3 domains.

Answer 24

True

Question 25

What can adaptor proteins contain that may serve as docking sites for other signaling proteins with SH2 domains?

Answer 25

tyrosine residues

Question 26

What is the mechanism of adaptor proteins in T cell activation?

Answer 26

1) LAT is phosphorylated and recurits PLCgamma and the GADS adaptor 2) SLP-76 (proline-rich stretch) associates with GADS via SH3 domain and recruits VAV after being tyrosine-phosphorylated. 3) the VAV proteins are guanine nucleotide exchange factors (GEFs) for GTPases that activate actin cytoskeletal rearrangemtns and transcriptional alterations.

Question 27

What do activating immune receptors have?

Answer 27

separate polypeptide chains for recognition and associated signaling polypeptide chains that contain cytosolic ITAMs

Question 28

What do inhibitory immune receptors have?

Answer 28

in the immune system typically have ITIMs on the cytosolic portion of the same chain that uses its extracellular domain for ligand recognition

Question 29

What type of inhibitory receptor is found on B cells and myeloid cells?

Answer 29

Fc-gamma-RIIB

Question 30

In TCR and BCR signaling, what causes activation of an associated Src family kinase?

Answer 30

Ag binding and clustering

Question 31

What esposes the tyrosine residues of a ITAM motif in TCR and BCR signaling?

Answer 31

conformational change unfolds the cytoplasmic tail of receptor to expose the tyrosine residues of a ITAM motif

Question 32

After activation of an associated Src family kinase due to Ag binding and clustering, what does the Src tyrosine kinase phosphrylate?

Answer 32

available tryosines in the ITAMs that was exposed do to the conformational change of the cytoplasmic tail of the receptor

Question 33

How many SH2 domains does Syk tyrosine kinase have that bind to a ITAM phosphotyrosine?

Answer 33

has tandem SH2 domains

Question 34

What do activated Syk kinases do?

Answer 34

phosphorylate adaptor proteins and enzymes that activate downstream signaling pathways of the immune receptor

Question 35

What is the number of ITAMs phosphorylated a measure of?

Answer 35

cytosolic interpretation of Ag affinity to the TCR

Question 36

What results in increasing numbers of phosphorylated ITAMs?

Answer 36

stronger or prolonged binding of Ag to the TCR

Question 37

True or False: Ag affinity of TCR can influence the nature of the cellular response at different stages of differentiation and activation.

Answer 37

True

Question 38

What is required for positive selection of T cells in the thymus?

Answer 38

weak TCR signals

Question 39

What kind of signal results in negative selection of T cells and their death by apoptosis in the thymus?

Answer 39

strong TCR signals

Question 40

What is a coreceptor?

Answer 40

transmembrane signaling protein on a lymphocyte that can facilitate Ag receptor activation

Question 41

What can the coreceptor with its signaling enzymes do?

Answer 41

increase ITAM phosphorylation and activation of the Ag receptor

Question 42

What are CD4 and CD8 on T helper and cytotoxic T cells, respectively?

Answer 42

coreceptors

Question 43

What is the coreceptor on B cells?

Answer 43

CR2/CD21

Question 44

What is an example of costimulation in the activation of T cells?

Answer 44

CD28-CD80/86

Question 45

In the modulation of signaling by inhibitory receptors, give an example of T cell receptor inhibition.

Answer 45

CTLA-4 (analog CD28)

Question 46

What are inhibitory receptors in B cells?

Answer 46

CD22 and Fc-gamma-RIIB