Modular Signaling Proteins

Question 1

Tyrosine Kinase Families

Answer 1

Src, Syk, Tec

Question 2

Src

Answer 2

c-Src, Lck, Fyn, Lyn

Question 3

Syk

Answer 3

Syk and Zap-70

Question 4

Tec

Answer 4

Tec, Btk, Itk

Question 5

Binding domains of the Src family

Answer 5

Unique domain, SH2, SH3, Kinas domain

Question 6

Binding domains of the Syk family

Answer 6

two SH2 domains

Question 7

Binding domains of the Tec family

Answer 7

PH domain, SH2, SH3, a proline peptide

Question 8

SH2 domain –>

Answer 8

binds phosphotyrosine

Question 9

SH3 domain –>

Answer 9

binds proline rich peptides

Question 10

PH –>

Answer 10

recognizes PIP3 and other phosphatidylinositol-derived lipids

Question 11

What kind of amino acids will Syk and Zap-70 bind to?

Answer 11

phosphotyrosine motifs

Question 12

Pleckstrin homology

Answer 12

recognizes specific phospholipids

Question 13

Btk

Answer 13

recognizes phosphatidylinositol triphosphate (PIP3)

Question 14

LAT

Answer 14

integral membrane protein that functions as an adaptor protein in T cell activation

Question 15

How does LAT work?

Answer 15

LAT is phosphorylated and serves as a binding site for adaptor proteins intracellularly (think proteins with SH2/SH3 domains etc)

Question 16

Fc(Epsilon)RI

Answer 16

IgE receptor

Question 17

Fc(gamma)RIIB

Answer 17

inhibitory receptor for B cells

found ON B cells and myeloid cells

Question 18

ITAMs

Answer 18

an associated signaling polypeptide in the cytoplasm

ITAMs activates after signals from Ag-receptors

“immunoreceptor tyrosine based activating motifs”

Question 19

ITIMs

Answer 19

inhibitory receptors in the immune system

usually on the cytosolic side of the same molecule whose extracellular side does the recognition

immunoreceptor tyrosine inhibitory motifs

Question 20

What is structurally different between the ITIM and the ITAM?

Answer 20

ITIMs are usually on the same molecule that receives the inhibitory signal, while ITAMs are on separate polypeptides to the activating receptor

Question 21

which would have an ITIM: Fc(epsilon)RI or Fc(gamma)RIIB

Answer 21

Fc(gamma)RIIB

Question 22

the Signaling Cascade involving the major signaling families, their roles.

Answer 22

both BCR/TCR use similar system

Ag-bin. causes receptor clustering -> activation of Src fam

Src fam phosphorylates ITAMs on receptor cytosolic side
Phosphorylated ITAMS attracts Syk family tyrosine kinase

Syk tyrosine kinases tandem SH2 domains bind ITAM
Syk activation causes downstream phosphorylations

Question 23

TCR to ITAMs ratio

Answer 23

6/10

Question 24

the stronger/prolonged binding of TCRs –>

Answer 24

increased activation of ITAMs

Question 25

ITAM phosphorylation is what

Answer 25

a cytosolic interpretation of Ag affinity

Question 26

what are the co-receptors of B cells and TCRs

Answer 26

CD4 and CD8 are the co-rec for TCRs
CR2/CD21 is the coreceptor for B cells

CR2 = complement receptor

Question 27

CTLA-4

Answer 27

analog of CD28: inhibitory coreceptor for TCRs

Question 28

CD22

Answer 28

inhibitory coreceptor of B cell

Question 29

inhibitory coreceptors of TCRs and BCRs

Answer 29

TCRs = CTLA-4 
BCR = Fc(gamma)RIIB, CD22