cells13-signaling3-2009

cells13-signaling3-2009 - Bio 106 Cells Lecture 13...

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Unformatted text preview: Bio 106 Cells Lecture 13 10/6/2009 Signaling Responses The mechanism to turn OFF G-protein pathways is: Remove the GTP B. Convert GDP to GTP GDP to GTP C. Convert GTP to GDP D. Convert ATP to ADP E. Remove ATP A. ECB3 16-7 Phospholipase C Produces Two Signals: IP3 and Ca++ N PIP2 C DAG Predict how the Ca++ signal is removed: PKC PKC phosphorylates cell proteins Ionophores are artificial ion channels – useful experimentally ECB2 16-25 IP3 Releases Ca2+ from the ER Hydrolyze GTP to GDP on phospholipase phospholipase C B. Breakdown IP3 C. Ca-ATP pumping of Ca++ into ER D. Breakdown of phospholipase C E. Answers A + B + C A. Fertilization Triggers An Increase in Ca++ Concentration Calmodulin A multipurpose intracellular Ca2+ receptor, mediating many Ca2+-regulated processes. The activated Ca2+calmodulin complex binds to a variety of protein kinases. CalmodulinCalmodulin-dependent protein kinase Movie 16.5 Cooper 15.28 MBOC3 15-34 Starfish egg that had been injected with a ECB2 16-26 fluorescent tracking dye for Ca++ is fertilized (arrow) and changes in [Ca++] tracked over time. Movie 16.4 Professor Owen Fall 2009 1 Bio 106 Cells Lecture 13 10/6/2009 Amplification Steps Many G-protein molecules activated by 1 activated receptor Each enzyme synthesizes many 2nd messages The 2nd messages activate a protein kinase Each G activates an enzyme The protein kinases activate many target enzymes Each enzyme synthesizes many 2nd messages MBOC3 15-42 The target enzymes produce many molecules of product Olfactory Pathway Smell Anything??? MBOC3 15-37 • Olfactory receptor neurons recognize odorants by specific G-protein-linked olfactory receptors G-protein• Odor binds, activates olfactory-specific G-protein olfactoryG(Golf), which activates adenylyl cyclase • cAMP opens cAMP-gated cation channels, which cAMPallows influx of Na+ • Na+ depolarizes membrane to create nerve impulse Vision Pathway MBOC3 15-41 Vision Pathway MBOC3 15-41 Rhodopsin is a G-proteincoupled receptor with 7 -helices Rhodopsin is a G-proteincoupled receptor with 7 -helices ECB316-28 ECB316-28 ECB316-29 Rod photoreceptor Rod photoreceptor ECB316-29 Professor Owen Fall 2009 2 Bio 106 Cells Lecture 13 10/6/2009 Receptor Tyrosine Kinases (RTKs) Some signaling receptors do NOT associate with G-proteins to turn on an enzyme. Many diseases, especially cancer, are linked to abnormalities in this pathway. Receptor Tyrosine Kinase Activates Phospholipase C During Sea Urchin Fertilization Proteins on the sperm surface activate the tyrosine kinase receptor This receptor. This activates activates the phospholipase C enzyme to cleave PIP2 to IP3 and DAG. The IP3 releases Ca2+. From Gilbert, 2000 Enzyme-coupled receptors acts as a kinase enzyme itself or complexes with another protein ECB3 16-30 that acts as an enzyme. If the G-protein we’ve examined is considered a trimeric protein, how many subunits would a monomeric G-protein have? Many RTKs Activate the Monomeric GTPase Protein Ras 0 B. 1 C. 2 D. 3 E. 4 A. Movie 16.6 Note the receptor activates proteins which then cause the exchange of GDP/GTP on Ras Mutant ras The mechanism to turn OFF Ras is: Remove the GTP B. Convert GDP to GTP GDP to GTP C. Convert GTP to GDP D. Convert ATP to ADP E. Remove ATP A. Professor Owen Fall 2009 3 Bio 106 Cells Lecture 13 10/6/2009 How Do We Know? Ras Activation of MAP-Kinase How Do We Know? Genetic analysis using mutants shows the order in which signaling proteins act in a pathway (hypothetical pathway shown). How Do We Know? Notch Signaling Notch Signaling S S 4 Professor Owen Fall 2009 Bio 106 Cells Lecture 13 10/6/2009 Mammalian Signaling Network Cooper 15.52 Professor Owen Fall 2009 5 ...
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