Immunobiology: The Immune System in Health & Disease Sixth Edition 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
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Antigen receptor signaling Multisubunit complexes Tyrosine phosphorylation Src-family PTK Signaling modules ITAM Syk-family PTK Scaffolding molecules SPACE and TIME!
Multisubunit complexes Figure 6-9
Tyrosine phosphorylation ATP ADP PROTEIN KINASE O - -O P O - O OH Protein Phosphorylated Protein serine threonine or tyrosine side chain 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
3BP2 SH2 PH SH3 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
(Immunoreceptor Tyrosine-based Activation Motif) ITAM (Immunoreceptor Tyrosine-based Activation Motif) Y x x L x (6-8) Y x x L V V
Signaling adaptors D D D D EC TM IC FcRg D ITAM D CD3z ITAM ITAM ITAM KARAP/ DAP12 D ITAM D DAP10 YxxM
Syk-family PTK
Scaffolding molecules LAT is a critical adaptor molecule required for TCR-mediated signaling and thymocyte development. Lck ZAP-70
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Coincidence detectors Context detectors CD4/CD8 co-receptor TCR co-stimulators co-inhibitors integrins Coincidence detectors output decoding