8536d_ch10_221 8/27/02 1: 37 PM Page 230 Mac 109 Mac 109: 1254_BpLGoldsby et al./Immunology 5e 230 PART I1 Generation of B-Cell and T-Cell Responses LE 10-2 Time course of gene expression by TH cells following interaction with antigen Time mRNA Ratio of activated to Gene product Function expression begins Location nonactivated cells MMEDIATE Protooncoger 5 min Nucleus >100 c-Jun Cellular oncogene; 15-20mn Nucleus transcription factor NFAT Transcription factor 20 min Nucleus Cellular oncogene 30 min Nucleus NF-KB Transcription factor 30 min Nucleus >10 EARLY tokine 30 min 100 45 min 1000 Insulin receptor Hormone receptor 1-2h TGF-B <2h IL2 receptor(p55 Cytokine receptor 50 TNF-R 1-3h >100 4-6h >10 IL-4 ccc <6h >100 IL-5 <6h <6h c-Myb 6 h 100 GM-CSF Cytokine 20h Secreted LATE HLA-DR lI MHC molecule 3-5 days VLA-4 100 VLA-1,ⅥLA2,VLA3,ⅥLA5 Adhesion molecules 7-14 days Cell membrane >100,?,?, SOURCE: Adapted from G. Crabtree, Science 243: 357 a Signal transduction begins with the interaction between a signal and its receptor. Signals that cannot penetrate the hydrolysis of GTP or exchange for GDP turns off the cell membrane bind to receptors on the surface of the signal by returning the G protein to an inactive form. cell membrane. This group includes water-soluble There are two major categories of G proteins. Small G signaling molecules and membrane-bound ligands proteins consist of a single polypeptide chain of about (MHC-peptide complexes, for example). Hydrophobi 21 kDa. An important small G protein, known as Ras, signals, such as steroids, that can diffuse through the cell is a key participant in the activation of an importan embrane are bound by intracellular receptors. proliferation-inducing signal-transduction cascade triggered by binding of ligands to their receptor tyrosine Signals are often transduced through G proteins, kinases. Large G proteins are composed of a,B, and Y membrane-linked macromolecules whose activities subunits and are critically involved in many processes, controlled by binding of the guanosine nucleotides GTP including vision, olfaction, glucose metabolism, and and gDP which act as molecular switches. Bound GTP phenomena of immunological interest such as leukocyte turns on the signaling capacities of the G protein■ Signal transduction begins with the interaction between a signal and its receptor. Signals that cannot penetrate the cell membrane bind to receptors on the surface of the cell membrane. This group includes water-soluble signaling molecules and membrane-bound ligands (MHC-peptide complexes, for example). Hydrophobic signals, such as steroids, that can diffuse through the cell membrane are bound by intracellular receptors. ■ Signals are often transduced through G proteins, membrane-linked macromolecules whose activities are controlled by binding of the guanosine nucleotides GTP and GDP, which act as molecular switches. Bound GTP turns on the signaling capacities of the G protein; hydrolysis of GTP or exchange for GDP turns off the signal by returning the G protein to an inactive form. There are two major categories of G proteins. Small G proteins consist of a single polypeptide chain of about 21 kDa. An important small G protein, known as Ras, is a key participant in the activation of an important proliferation-inducing signal-transduction cascade triggered by binding of ligands to their receptor tyrosine kinases. Large G proteins are composed of , , and subunits and are critically involved in many processes, including vision, olfaction, glucose metabolism, and phenomena of immunological interest such as leukocyte chemotaxis. 230 PART II Generation of B-Cell and T-Cell Responses TABLE 10-2 Time course of gene expression by TH cells following interaction with antigen Time mRNA Ratio of activated to Gene product Function expression begins Location nonactivated cells IMMEDIATE c-Fos Protooncogene; 15 min Nucleus  100 nuclear-binding protein c-Jun Cellular oncogene; 15–20 min Nucleus ? transcription factor NFAT Transcription factor 20 min Nucleus 50 c-Myc Cellular oncogene 30 min Nucleus 20 NF-B Transcription factor 30 min Nucleus  10 EARLY IFN- Cytokine 30 min Secreted  100 IL-2 Cytokine 45 min Secreted  1000 Insulin receptor Hormone receptor 1 h Cell membrane 3 IL-3 Cytokine 1–2 h Secreted  100 TGF- Cytokine  2 h Secreted  10 IL-2 receptor (p55) Cytokine receptor 2 h Cell membrane  50 TNF- Cytokine 1–3 h Secreted  100 Cyclin Cell-cycle protein 4–6 h Cytoplasmic  10 IL-4 Cytokine  6 h Secreted  100 IL-5 Cytokine  6 h Secreted  100 IL-6 Cytokine  6 h Secreted  100 c-Myb Protooncogene 16 h Nucleus 100 GM-CSF Cytokine 20 h Secreted ? LATE HLA-DR Class II MHC molecule 3–5 days Cell membrane 10 VLA-4 Adhesion molecule 4 days Cell membrane  100 VLA-1, VLA-2, VLA-3, VLA-5 Adhesion molecules 7–14 days Cell membrane  100, ?, ?, ? SOURCE: Adapted from G. Crabtree, Science 243:357. 8536d_ch10_221 8/27/02 1:37 PM Page 230 Mac 109 Mac 109:1254_BJN:Goldsby et al. / Immunology 5e: