Slide 1Signal TransductionSignal TransductionSignal TransductionSignal TransductionSignal TransductionSignal TransductionSignal TransductionSignal TransductionSignal TransductionSignal TransductionSignal TransductionSignal TransductionPage 1Signal TransductionLehninger Readings Chapter 12 pages 419-457At the end of this section you should be able to dissect signaling pathways by identifying the various parts of the pathway, explaining the roles of each part, and predicting how perturbations of the pathway’s components will alter signaling through the pathway and how this will alter cellular outcomes.Student Learning ObjectivesYou should be able to: 1) Tell the "Big Picture" story of why signal transduction is needed and how it happens.2) Describe four general features of signal transduction. 3) Explain the generic process of signal transduction and the generic role of the components in this process.4) List the basic characteristics of the six general types of signal receptors used in cells.5) Compare and contrast the structures of gated channels, receptor tyrosine kinases, G protein-coupled receptors, and steroid hormone receptors. 6) Compare and contrast the mechanism by which gated channels, receptor tyrosine kinases, G protein-coupled receptors, and steroid hormone receptors initiate signaling.7) Analyze epinephrine signaling in liver cells applying general principles of signal transduction to this system.8) Explain the general role of second messengers in signal transduction, list common second messengers, and explain their role in specific signal transduction pathways.9) Discuss the role of multivalent proteins in signal transduction.10) Explain the role of enzymes in forming and degrading second messengers.11) Analyze insulin regulated gene expression applying general principles of signal transduction to this system.12) Explain a phosphorylation cascade and the role of these cascades in signal transduction.13) Analyze neural signal transduction applying general principles of signal transduction to this system.14) Analyze steroid hormone regulated gene expression applying general principles of signal transduction to this system.15) Analyze additional real and hypothetical pathways applying general principles of signal transduction to determine the role of each component of the pathway.16) Predict how perturbations of a pathway’s components will alter signaling through the pathway and how this will alter cellular outcomes.Page 2Signal Transduction•General features of signal transduction systems–Specificity–Sensitivity•High Affinity•Cooperative Binding•Amplification–Desensitization–IntegrationFigure 12-11) Tell the "Big Picture" story of why signal transduction is needed and how it happens.2) Describe four general features of signal transduction.Page 3Signal Transduction•General Process–Signal (1st Messenger)–Receptor–Signal Transduction•2nd Messenger(s)–Diffusible molecules•Phosphorylation Cascades–Cellular Targets•Regulated Enzymes in Pathways•Transcription Factors–Change gene expression–Cellular response–Signal TerminationFigure 12-26Figure 12-15Figure 12-10Figure 12-303) Explain the generic process of signal transduction and the generic role of the components in this process.Page 4Signal Transduction•Six general types of receptors–G protein-coupled Receptors (serpantene receptor)•7 transmembrane alpha helixActivate G-proteins–Receptor Tyrosine Kinases•Dimers- single transmembrane helix•Activate tyrosine kinase domain inside the cell–Gated Ion Channels•Channels- ligand or voltage change opens or closes channel–Steroid Receptors•Inside cell (cytosol/nucleus) 1st messenger diffuses into the cell, change gene expression–Receptors Guanylyl Cyclases–Adhesion receptors4) List the basic characteristics of the six general types of signal receptors used in cells.5) Compare and contrast the structures of gated channels, receptor tyrosine kinases, G protein-coupled receptors, and steroid hormone receptors. 6) Compare and contrast the mechanism by which gated channels, receptor tyrosine kinases, G protein-coupled receptors, and steroid hormone receptors initiate signaling.Figure 12-2Page 5Signal Transduction•-Adrenergic Receptor (G protein-coupled receptors)–Epinephrine (Signal)•Original signal (epinephrine binding to receptor)–-Adrenergic Receptor–G protein- trimer (alpha beta and gamma)•Release alpha and then beta-gamma together–Adenylyl Cyclase- enzyeme that converts AMP to c-AMP–cAMP (2nd Messenger)-Figure 12-47) Analyze epinephrine signaling in liver cells applying general principles of signal transduction to this system.8) Explain the general role of second messengers in signal transduction, list common second messengers, and explain their role in specific signal transduction pathways.9) Discuss the role of multivalent proteins in signal transduction.10) Explain the role of enzymes in forming and degrading second messengers.Figure 12-4Page 6Signal Transduction•-Adrenergic Receptor (G protein-coupled receptors)–Protein Kinase A•PKA •2 Catalytic Subunits•2 Regular Subunits–Cellular Response–AmplificationFigure 12-7Figure 12-6Page 7Signal Transduction•-Adrenergic Receptor (G protein-coupled receptors)–Termination•G proteins–Bind to GDP/GTP»Act as switch and timer–Switch»GDP bound -inactive»GTP bound-active»GEF (guanine nucleotide exchange factor)–Timer»Hydrolyzes GTP  GDP»Very very slow, ~5/s»GAP- interact with G-protein and speed up process•Phosphodiesterases –Break down cAMP•Phosphatases–Remove phosphates»Terminate signalingFigure 12-5Figure 12-5Figure 12-4Page 8Signal Transduction•-Adrenergic Receptor (G protein-coupled receptors)–Termination•DesensitizationFigure 12-8Page 9Signal Transduction•Different Signal Transduction Cascades Mix and Match Components–Other G-proteins•G(s-alpha)- activates adenylyl cyclase•G(I alpha)- inhibits adenylyl cyclase•G(q alpha)- activates PLC•Transducin- activates a phosphodiesterase–Other 2nd Messengers•IP3•DAG•Ca++–Examples of “Mix and Match”Figure 12-10Figure 12-43Page 10Signal Transduction•G protein inhibitors–Cholera Toxin–Pertussis Toxin•Multivalent Proteins–AKAPs•A Kinase anchoring proteins–Other Examples•SH2 domain binds phosphate-Tyr•SH3 domain binds to PIP3Page 443Figure 12-9Figure 12-23Page 11Signal Transduction•Insulin Regulation of Gene