Lect_13_notes - as much as 1 million fold by this signal...

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Lecture 13 Cell Signaling Prof. Schlissel Bio 1A Feb. 22, 2008 Cell Signaling: An Overview 1. The big picture: ligands (signaling molecules) bind to receptors, receptors activate transduction molecules within the cytoplasm, and these transducers change gene expression, metabolism, and the cytoskeleton. 2. Types of receptors—ligand-gated ion channels; G-protein coupled receptors (GPCRs); steroid hormone receptors; enzyme-linked transmembrane proteins (often kinases). 3. Example of GPCR—Epinephrine response. Ligand binds receptor, results in activation of G-protein. GTP-bound G-protein binds to adenyl cyclase, activating its activity. Adenyl cyclase converts ATP into cAMP. cAMP binds to protein kinase A (PKA), activating it. PKA activates phosphorylase kinase by phosphorylating it. The active kinase then phosphorylates glycogen phosphorylase, activating it to convert glycogen to glucose and start glycolysis. Signal from the initial activation of the GPCR is amplified
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Unformatted text preview: as much as 1 million fold by this signal transduction cascade since each step involves enzymes which convert many substrates. 4. Example of a receptor tyrosine kinase. Ligand causes dimerization of receptor, activating its kinase activity. It auto-phosphorylates. Phosphorylated cytoplasmic domain binds to other signaling molecules including PI-3 kinase, GAP, and phospholipase C. GAP activates a G-protein. PI-3 kinase phosphorylates inositol phosphate, a membrane phospholipids. PLC hydrolyzes PIP2 into IP3 and DAG. IP3 binds to Ca2+ channel in ER membrane, releasing Ca2+ into cytoplasm. DAG binds to protein kinase C (PKC) along with Ca2+, activating its kinase activity. 5. Signal transduction is a complex web of regulated protein-protein interactions which produce second messengers and activate signal transducing enzymes, ultimately regulating gene expression, metabolism, and the cytoskeleton....
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