Signal Transduction Lehninger Readings Chapter 12 pages 419 457 At 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 Objectives You 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 1 Signal Transduction 1 2 Tell the Big Picture story of why signal transduction is needed and how it happens Describe four general features of signal transduction General features of signal transduction systems Specificity Sensitivity High Affinity Cooperative Binding Amplification Desensitization Figure 12 1 Page 2 3 Signal Transduction Explain the generic process of signal transduction and the generic role of the components in this process General Process Signal 1st Messenger Receptor Signal Transduction 2nd Messenger s Diffusible molecules Figure 12 26 Figure 12 15 Phosphorylation Cascades Cellular Targets Regulated Enzymes in Pathways Figure 12 10 Transcription Factors Change gene expression Cellular response Figure 12 30 Page 3 Signal Transduction Figure 12 2 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 proteincoupled 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 Six general types of receptors G protein coupled Receptors serpantene receptor 7 transmembrane alpha helix Activate 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 Page 4 Signal Transduction 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 Figure 12 4 Adrenergic Receptor G proteincoupled 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 4 Page 5 Signal Transduction Adrenergic Receptor G proteincoupled receptors Protein Kinase A PKA 2 Catalytic Subunits 2 Regular Subunits Figure 12 6 Cellular Response Amplification Figure 12 7 Page 6 Signal Transduction Adrenergic Receptor G proteincoupled receptors Termination G proteins Bind to GDP GTP Act as switch and timer Figure 12 5 Figure 12 5 Figure 12 4 Switch GDP bound inactive GTP bound active GEF guanine nucleotide exchange factor Timer Hydrolyzes GTP GDP Very very slow 5 s GAP interact with Gprotein and speed up process Phosphodiesterases Break down cAMP Phosphatases Remove phosphates Terminate signaling Page 7 Signal Transduction Figure 12 8 Adrenergic Receptor G protein coupled receptors Termination Desensitization Page 8 Signal 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 Figure 12 10 Examples of Mix and Match Figure 12 43 Page 9 Signal Transduction G protein inhibitors Cholera Toxin Pertussis Toxin Page 443 Multivalent Proteins Figure 12 9 AKAPs A Kinase anchoring proteins Figure 12 23 Other Examples Page 10 Signal Transduction 11 Analyze insulin regulated gene expression applying general principles of signal transduction to this system 12 Explain a phosphorylataion cascade and the role of these cascades in signal transduction Insulin Regulation of Gene Expression Receptor Tyrosine Kinase Insulin Signal Receptor Tyrosine Kinase Grb2 is a Multivalent Protein Ras is a G Protein Figure 12 15 Phosphorylation Cascade Amplification Cellular Response Note that insulin also mediates other cellular effects through branches in the signaling pathway Figure 12 8 Figure 12 14 11 Conformational Changes in thePage Insulin Signal Transduction 13 Analyze neural signal
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