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Unformatted text preview: Signal transduction http://www.temple.edu/stl/images/SignalTransduction.jpg 1 Last time Infrastructure of communication Extra-cellular structures Cell connections Communication signals - an overview Local and distance signaling 2 Signal transduction 1. Reception - signal molecule binds to receptor 2. Transduction - signal is transmitted to response element 3. Response - output of signal Conclusions - key points 3 The signal transduction pathway - an overview Reception Transduction Response Regulation of cellular activities Ligand Receptor "relay molecules" Fig. 11.5 4 Reception Signaling molecule ("ligand") transiently binds receptor (non-covalently) Receptor can be: - in the cell = intracellular receptor - in the membrane = membrane receptor Often, a ligand binding a receptor will change the shape of the receptor protein 5 Ligand-receptor binding Ligand binding receptor will cause receptor to undergo conformational change Fig. 11.6 6 Two classes of receptors 1. Membrane bound receptors - located on surface of membrane, often transmembrane proteins 2. Intracellular receptors - located in cytoplasm or nucleus 7 Two types of ligands 1. Water soluble or polar ligands 2. Hydrophobic or very small molecular ligands 8 Intracellular receptor intracellular receptors can sometimes be `transcription factors', which bind DNA and turn genes on or off Fig. 11.6 9 Membrane receptors Three major families of receptors 1. G-protein linked receptor 2. Receptor tyrosine kinase 3. Ion channel receptors 10 G-protein linked receptor Fig. 11.7 11 G-protein linked receptor Involved in: sensory perception (sight, smell), diseases Fig. 11.7 12 Activation of G-protein linked receptor Fig. 11.7 13 Receptor tyrosine kinase Both a receptor and an enzyme: enzyme = kinase Works as a dimer Phosphorylates (adds phosphate) to neighboring receptor's tyrosine amino acids Fig. 11.7 14 Activation of Receptor Tyr Kinase 1 2 can activate up to 10 different signaling pathways at once! 3 Fig. 11.7 15 Ion channel receptors Commonly found in nervous system, in which the signal molecule is a neurotransmitter Fig. 11.7 16 Summary Reception - signal binds receptor Signal (or ligand) can be polar or nonpolar Receptor can be membrane protein or intracellular protein Three types of membrane receptors G-protein linked receptor Receptor Tyr kinase Ion channel receptor 17 Transduction Multistep pathway using molecules and proteins to transmit signal to response element - Amplifies signal - Signal itself is not transmitted 18 Signal is transduced by `relay molecules' Relay molecules are often proteins - change shape as signal is `carried' though pathway - often phosphorylation (attachment of phosphate groups to protein) is used to bring about the conformational change 19 Phosphorylation cascade Fig. 11.8 20 Second messengers These relay molecules are NOT proteins Broadcast signal! Common second messengers - cAMP +2 Ca 21 cAMP activates a kinase kinase phosphorylates (adds phosphate group to) a target protein target protein activity changes 22 Fig. 11.10 23 Cholera Vibrio cholerae in drinking water - secretes toxin - toxin modifies G-protein - G-protein involved in salt and water secretion - G-protein now unable to hydrolyze GTP to GDP = always active! - G-protein permanently signals - cAMP intestines secrete water continuously 24 http://web.mit.edu/people/tprester/dtm2001/msf_moz_cholera_camp.jpg Erectile disfunction cGMP also second messenger - relaxes smooth muscle - converted to inactive GMP quickly Viagra - slows conversion of cGMP to GMP - smooth muscle stays relaxed longer - more blood can enter blood vessels 25 +2 Ca as second messenger 26 Summary Signal transduction - transmits signal from receptor to response element Signal can be carried by relay proteins, which undergo conformational change - usually because phosphorylated Signal can be carried by second +2, IP ) messengers (cAMP, Ca 3 Signal itself is not carried 27 Response Output of signal - results in regulation of cellular activities - can occur in cytoplasm or nucleus 28 Response 29 Summary Response stage is the output of the signal - regulation of cell activities - changes in cytoplasm or turning genes on or off 30 Key Points 1. Signal transduction pathway amplifies signal 2. Signaling can be very specific (Fig. 11.15) 3. These are networks of interactions, not linear pathways 4. Each signal or activated relay protein must be transient so cell can continue to respond to new environmental cues 5. Reversibility - active state must be reset (phosphorylation - dephosphorylation, cAMP to AMP, GTP to GDP, Ca+2 gradients reestablished) 31 Summary Reception - signal molecule binds to receptor - three kinds of receptors Transduction - signal is transmitted to response element - conformational change in proteins - second messengers Response - output of signal - regulation of cellular activities Conclusions - key points 32 Next Time Energy and material flow 33 ...
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This note was uploaded on 05/06/2008 for the course BIO 311C taught by Professor Satasivian during the Spring '08 term at University of Texas at Austin.
- Spring '08