Immunobiology: The Immune System in Health & Disease Sixth Edition Chapter 6 Signaling Through Immune System Receptors Copyright © 2005 by Garland Science Publishing Charles A. Janeway, Paul Travers, Mark Walport, Mark Shlomchik

Figure 6-16

Figure 6-15 part 1 of 2

Antigen receptor signaling Multisubunit complexes Tyrosine phosphorylation Src-family PTK Signaling modules ITAM Syk-family PTK Scaffolding molecules SPACE and TIME!

Figure 6-9 Multisubunit complexes

Figure 7-21 part 1 of 3

Figure 7-21 part 2 of 3

Figure 7-21 part 3 of 3

ATP ADP Phosphorylated Protein PROTEIN PHOSPHATASE PROTEIN KINASE Protein serine threonine or tyrosine side chain O -  - O  P  O -  O OH Pi Tyrosine phosphorylation

Figure 6-11 part 1 of 2 Src-family PTK

Protein Phospho-Protein Protein Phosphatases Protein Kinases SH2 domain Signaling modules

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 SH2 PH SH3 3BP2

Yxx Lx (6-8) Yxx L V V ITAM (Immunoreceptor Tyrosine-based Activation Motif)

ECTMIC D D ITAM ITAM FcR  KARAP/DAP12 Signaling adaptors D YxxM DAP10 D ITAM ITAMITAM CD3 

Syk-family PTK

Lck ZAP-70 LAT is a critical adaptor molecule required for TCR-mediated signaling and thymocyte development. Scaffolding molecules