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Published byAlaina Singleton Modified over 9 years ago
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Last lecture: reversible phosphorylation regulation of transcription This lecture: signal transduction
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Fridays MC H313 Biological Sciences Seminar Series This Friday (19th): The smallest hormone: birth, life and many deaths of nitric oxide
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Intracellular signal transduction:
receptors or sensors second messengers kinases, phosphatases, transcription factors downstream targets (proteins)
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Intracellular Signal Transduction
Hormone receptors within the cell
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Intracellular receptors:
- cytosolic - nuclear
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T4 T3
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Intracellular Signal Transduction
Hormone receptors within the cell Hormone receptors on cell membrane (facing external environment)
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2. Membrane receptors: - laterally mobile - interact with other membrane proteins - catalytic
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Intracellular Signal Transduction
Hormone receptors within the cell Hormone receptors on cell membrane (facing external environment) Signaling of entirely intracellular events
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3. Detection & signaling of entirely intracellular events
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ATP synthetic processes
ATP ADP AMP ↑work → ↑[AMP] AMP kinase ATP synthetic processes
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Intracellular Signal Transduction
Hormone receptors within the cell Hormone receptors on cell membrane (facing external environment) Signaling of entirely intracellular events
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Roles of signal transduction?
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Roles of signal transduction
(1) Permit adaptation (2) Regulate response (3) Coordinate related events
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Features of signal transduction
2. Amplification 3. Diversification 4. Transience
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Features of signal transduction
1. Transduction - conversion of one form to another 2. Amplification 3. Diversification 4. Transience
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Features of signal transduction
1. Transduction - conversion of one form to another 2. Amplification - one receptor/binding event can affect big changes 3. Diversification 4. Transience
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Features of signal transduction
1. Transduction - conversion of one form to another 2. Amplification - one receptor/binding event can affect big changes 3. Diversification - may affect related but different targets 4. Transience -
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Features of signal transduction
1. Transduction - conversion of one form to another 2. Amplification - one receptor/binding event can affect big changes 3. Diversification - may affect related but different targets 4. Transience - can be turned off
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An example of signal transduction: Receptors & G-proteins
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G-protein activated by binding GTP
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1. Receptors that activate G-proteins
Largest family of receptors on cell surface (>1000 members) Egs. epinephrine (adrenergic) receptor Heterotrimers (one each of α, β, γ subunits) Interact with a variety of effector molecules Depend on lateral mobility of proteins in membrane
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Eg. G-protein acting via adenylyl cyclase (AC)
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In the cytosol:
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Mobilization of glucose subunits from glycogen:
Hormone + receptor → G-protein → adenylyl cyclase → cAMP↑ → PKA → phosphoprotein kinase → glycogen phosphorylase
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G-proteins associated with phospholipase C and protein kinase C
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G-proteins can: Be stimulatory or inhibitory (eg. differential response to epinephrine) Have different actions; depends on: - particular combination of subunits (16 possible α isoforms; 5β; 11γ ) - presence of effectors nearby (egs. AC, phosphodiesterase, phospholipase) Affect changes in cAMP, Ca2+, diacylglycerol
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Receptors that are enzymes
Tyrosine kinases Guanylyl cyclases Catalyze cleavage (proteolysis) reactions (these may release an active transcription factor)
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Example 1: the insulin receptor
Heterotetramer (2α and 2β subunits) β subunit is tyrosine kinase (autophosphorylates tyrosines on receptor, then on other proteins) Active IR stimulates PI 3-kinase activity GLUT4 protein recruited to membrane from intracellular vesicles
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Example 2: Nitric oxide receptor
Has guanylyl cyclase activity: GTP → cGMP
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Protein regulation and signal transduction - summary and overview
Many strategies for altering specific and cellular activities Fast vs slow responses Specific activity vs amount of a protein Protein kinases/phosphatases Many transcription factors and HREs Receptors: membrane, cytosol, nucleus Receptor – effector mechanisms Second messengers: signal amplification and/or diversification (egs. Ca++, cAMP, cGMP)
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Read chapter 3 for Thursday
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