bis_104_camp_signaling_fall_08 - G-protein 3 G-protein...

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BIS 104 CELL SIGNALING Model system #1: cAMP as second messenger for glucose mobilization in liver cells. Liver cells store glucose in the form of a polymer, glycogen. The cells have two different transmembrane receptor proteins that are stimulated either by epinephrine (secreted by adrenal gland) or by glucagon, a peptide hormone secreted by alpha cells of the pancreas. The end point of this signaling pathway is the phosphorylation of glycogen by the enzyme phosphorylase to create glucose -1 phosphate, which then is converted to glucose and exported from the cell into the blood stream (GLUT transporters). The cascade of interactions that occurs between the initial ligand binding and the ultimate glucose export is mediated by a cAMP signaling pathway (See figure 15.12, p 630). 1. Ligand binds to receptor outer leaflet domain. 2. Receptor conformation changes and inner leaflet domain is now bound by a
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Unformatted text preview: G-protein. 3. G-protein / receptor complex activates the enzyme adenylyl cyclase (still on inner leaflet) 4. Adenylyl cyclase converts ATP into cAMP. 5. cAMP diffuse away; binds to and activates Protein Kinase A (PKA). 6. PKA has two main effects: it inhibits glycogen synthetase and activates phosphorylase kinase. 7. Phosphorylase kinase activates phosphorylase (adds PO 4- to a serine) 8. Phosphorylase acts on glycogen to make glucose-1 phosphate; other enzymes convert glu-1-P to glucose. Signal pathway is turned off by phosphatase-1 and by cAMP phosphodiesterase . Protein Kinase A also enters nucleus and activates a transcription factor (CREB: c AMP R esponse E lement B inding protein). This results in the production of enzymes that catalyze the synthesis of glucose from precursors. See Table 15.4, p. 631 for a list of hormone-induced responses mediated by cAMP....
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This note was uploaded on 10/20/2009 for the course BIS 104 taught by Professor Scholey during the Winter '08 term at UC Davis.

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bis_104_camp_signaling_fall_08 - G-protein 3 G-protein...

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