Notes
Slide Show
Outline
1
Chapter 6:
Signaling through Immune System Receptors
2
Just a small sample of the fun that awaits:
  • Smac, Src, GEM, DIG, GPI, SH2, SH3, PLC-gamma, PIP2, IP3, DAG, GEF, PKC, RAS, ITAMs, Syk, Fyn, Blk, Lyn, Csk, Cbp, Cbl, Lck, PI 3 kinase, ZAP-70, LAT, SLP-76, BLNK, Tec kinases, PH domains, Shc, GADS, SOS, Grb2, Ras-GRP, MAPKs, etc…
  • A lot of detailed information,
  •  salient points will be emphasized
  • Be patient and specific with
  • questions
3
Part I. Overview of basic strategies of molecular signaling
  • Signal transduction, the basic problem addressed:


  • How to convert external receptor binding event -> across membrane -> into intracellular biochemical event
  • Common Properties: signal amplification, multiple levels with controls at each level


  • For lasting changes the ultimate destination is the nucleus and regulation of transcription


  • Results of signal transduction: changes in cytoskeleton, rearrangement of secretory apparatus, progression of the cell cycle, etc…
4
Clustering
  • Receptors - Conformational change upon binding their ligand (ion channels, enzyme-linked)
  • Clustering necessary -> allows association with intracellular proteins/enzymes (g-proteins, kinases, adaptor proteins, etc in BCR and TCR)
5
Figure 6-1
6
Figure 6-2
7
Figure 6-4
8
Figure 6-3
9
Figure 6-5
10
 
11
Figure 6-6
12
Figure 6-7
13
G-proteins
14
Part II: Antigen Receptor Structure and Signaling Pathway Specifics
  • The BCR and the TCR are multi-protein complexes composed of both variable antigen binding chains and “invariant” accessory chains.
  • The variable Ag binding chains lack substantial cytoplasmic tails for signaling; the accessory chains are necessary for 1.) transport of the antigen receptor to the cell surface and 2.) initiating signaling following binding of antigen.
  • Antigen binding in mature lymphocytes ultimately leads to activation of transcription factors which turn on certain genes and turn off inhibitory genes expressed in resting cells.
  • Pre-T and pre-T cell receptors (chapter 7) employ same accessory molecules for signal transduction in developing T and B progenitors.
15
Figure 6-8
16
Figure 6-9
17
Figure 6-10
18
Figure 6-12
19
Figure 6-11
20
Figure 6-11
21
Figure 6-12
22
Figure 6-13
23
Figure 6-14
24
Figure 6-12
25
Figure 6-15
26
Figure 6-16
27
On to the Nucleus
28
Figure 6-17
29
Figure 6-18
30
 
31
 
32
 
33
Figure 6-19
34
 
35
Figure 6-20
36