CellSignaling08Lec2 - General Principles of Cell...

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General Principles of Cell Communication Altered Metabolism Altered cell Shape or movement Altered Gene expression Metabolic enzyme Intracellular signaling proteins Activate Extracellular signal molecule Receptor Protein Target Proteins Gene regulatory protein Cytoskeletal protein Signal Transduction pathway
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G-protein-linked Receptors
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G-Protein Linked Receptors Four parts to this pathway 1. Receptor – (Transmembrane protein) 2. GTP Binding protein (molecular switch) 3. Membrane bound effector protein that is activated by the G-protein. 4. Feedback regulation and desensitization.
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G-Protein Trimeric G protein. Composed of 3 polypeptides (subunits) Function in a similar fashion to MONOMERIC GTP-binding proteins (RAN). MOLECULAR SWITCH GDP
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Activated - GTP binding causes conformational change. Allows it to interact with its target (can activate or inhibit target). GDP GTP Activated – dissociation from α unmasks active domain, can transduce a signal by interacting with an effector protein. γ α β γ β α GTP
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ACTIVE GTP-bound state is short-lived . Intrinsic GTPase activity hydrolyzes GTP to GDP in minutes. Rate of GTP hydrolysis is enhanced by binding to the effector.
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Effector proteins All effector proteins in GPCR pathways are either : 1)ion channels or 1) enzymes that catalyze the formation of second messengers .
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What does cAMP do? Dependent on the Cell type. Almost all of the effects of cAMP are mediated through Protein Kinase A PKA
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PKA IS A SERINE/THREONINE KINASE. - will phosphorylate different proteins in different cell types. phosphorylate TFs, turn on or turn off specific gene transcription. phosphorylate metabolic enzymes themselves, inactivating or activating specific processes.
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PKA P P Glycogen Synthase ATP ATP ADP ADP ATP ADP Glycogen Phosphorylase kinase P Glycogen Phosphorylase Glycogen Glucose-1-P
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Stop Signal - Stop the reaction. Remove signal (epinephrine)
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CellSignaling08Lec2 - General Principles of Cell...

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