GW_SigTrans I.11.23 - ADVANCED CELL BIOLOGY/ MOLECULAR...

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1 ADVANCED CELL BIOLOGY// MOLECULAR BIOLOGY OF CELLS 01-146:470 + 16-148:514 •Monday 11.23.2009 (8:40-10:00) •SEC-118 Class web page: http://lifesci.rutgers.edu/~denhardt/course/cellmolbiol.htm •Dr. Guy Werlen •Dept. of Cell Biology & Neuroscience •Nelson Bio. Labs., B333 [email protected] •Office hours, Friday 3:30pm-5:00 pm Molecular Cell Biology 6th Edition Chapter 15: Cell signaling I: Signal transduction and short-term cellular responses Lodish • Berk • Kaiser • Krieger • Scott • Bretscher •Ploegh • Matsudaira - 15.1 From extracelluar signal to cellular response. - 15.2 Studying cell-surface receptors. - 15.3 Highly conserved components of intracelluar signal-transduction pathways. - 15.4 General elements of G protein-coupled receptor systems. - 15.6 G protein-coupled receptors that activate or inhibit adenylyl cyclase. - 15.7 G protein-coupled receptors that activate phospholipase C. From Extracellular signals to cellular responses From extracelluar signal to cellular response, or why signal transduction is a must 1) Synthesis and packaging of secreted molecules (ligands). 2) Exocytosis 3) Transport of ligand to target cell 4) Binding of ligand to receptor 5) Activation of intracellular signaling pathways. 6a) Short term modifications 6b) Long term modifications 7) Signaling inhibition (“feedback loop”) 8) Removal of ligand
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2 Close range, or far reaching signaling Distance: several meters Distance: a few micrometers Distance: “a slap on your face” Attached ligands can also induce signaling Ligands attached on one cell can trigger signaling in an adjacent target cell (adherence molecules such as integrins) Ligand-Receptor interactions: Harmonic “groove” Essential residues on the ligand and the receptor determine a specific binding. a) In this example only 8/28 aa of the hormone that are found at the binding interface of the hormone to the receptor are contributing 85% of the binding energy (pink in the cartoon). Similarly, while several aa of the receptor binding interface are important (yellow), 2 tryptophan (trp) residues (blue) contribute most of the energy for binding growth hormones. b) Binding of growth hormone to 1 receptor molecule is followed by binding of a 2 receptor (c; purple) to the opposing side of the hormone; this involves the same set of aa on the second receptor (yellow and blue in the cartoon), but different residues on the hormone. c) Hormone-induced receptor dimerization is a common mechanism for activation of receptors and the start of signal transduction. Studying cell surface receptors Specific signaling mechanisms exist downstream of distinct receptor families, but they are all activated by ligand binding to the receptor and their activation mainly leads to gene transcription.
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3 Dissociation constants (Kd) determine the affinities of specifics ligand-receptor interactions R+L RL k of k on Ligand (L) binding to a receptor (R) depends on the rate constant for formation ( k on )o fa receptor-ligand complex (RL) as well as its rate constant of dissociation ( k of ). At equilibrium, the rate of formation of the
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This note was uploaded on 09/02/2010 for the course BME 314 taught by Professor Frey during the Spring '08 term at University of Texas at Austin.

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GW_SigTrans I.11.23 - ADVANCED CELL BIOLOGY/ MOLECULAR...

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