Transcript Immunobiology: The Immune System in Health & Disease Sixth

Charles A. Janeway, Paul Travers, Mark Walport, Mark Shlomchik
Immunobiology:
The Immune System in Health & Disease
Sixth Edition
Chapter 6
Signaling Through Immune
System Receptors
Copyright © 2005 by Garland Science Publishing
Figure 6-16
Figure 6-15 part 1 of 2
Antigen receptor signaling
•
•
•
•
•
•
•
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Multisubunit complexes
Tyrosine phosphorylation
Src-family PTK
Signaling modules
ITAM
Syk-family PTK
Scaffolding molecules
SPACE and TIME!
Multisubunit complexes
Figure 6-9
Figure 7-21 part 1 of 3
Figure 7-21 part 2 of 3
Figure 7-21 part 3 of 3
Tyrosine phosphorylation
ATP
ADP
PROTEIN
KINASE
Protein
serine
threonine
or
tyrosine
side chain
O
-O  P  O - Phosphorylated
Protein

O
OH
PROTEIN
PHOSPHATASE
Pi
Src-family PTK
Figure 6-11 part 1 of 2
Signaling modules
Protein Phosphatases
Protein
Phospho-Protein
Protein Kinases
SH2 domain SH2 domain
SH2 domain SH2 domain
3BP2
Adaptor proteins
• Adaptor proteins contain modular
domains and lack intrinsic enzyme
activity
• Adaptors are scaffolds for the
organization of macromolecular
complexes
• Adaptors play an important role in
the integration and propagation of
cell signaling that lead to activation.
• They are integral membrane
proteins or cytosolic proteins:
TRAPs: Transmembrane Adapter
Proteins
CAPs: Cytoplasmic adapter
proteins
PH
SH3
SH2
ITAM
(Immunoreceptor Tyrosine-based Activation Motif)
Y
x
x
L
V
x (6-8) Y x
x
L
V
Signaling adaptors
EC
TM
IC
FcRg
D
CD3z
D
KARAP/
DAP12
D
ITAM
DAP10
D
YxxM
ITAM
ITAM
ITAM
ITAM
Syk-family PTK
Scaffolding molecules
LAT is a critical adaptor molecule required for
TCR-mediated signaling and thymocyte
development.
Lck
ZAP-70