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Lecture 12

Lecture 12 - Cell Signalling Part 2 - Feb 26.docx

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Department
Biology
Course
BIOL 2021
Professor
Patricia Lakin- Thomas
Semester
Winter

Description
February 26th, 2013 Chapter 15: Cell Signaling  Figure 15-26, 15-28abcd  Cell surface receptors, general properties, feedback loops  Positive Feedback: o Short term response becomes long-term change o Cell switches from one state to another= cell memory o Cell has memory of signal that used to be there  Even though signal goes away, cell stays activated because positive feedback keeps itself activated  Negative Feedback o Short delay= change detector o Long time delay= oscillations Adaptation  Figure 15-29  Refers to “desensitization” or using negative feedback with a short delay to turn down the response  Receptor sequestration: taking receptor into an endosome and thus into the cell, if it’s not on the plasma membrane it won’t cause a response  Down regulation  Receptor inactivation: ex phosphorylation  Inactivate signaling protein  Production of inhibitory protein G-Protein Coupled Receptors (GPCRs)  Figure 15-16b  Largest family of cell surface receptors  Signals from environment and other cells  700 GPCRs in human genome (many are called orphan receptors because we’re not sure what they do just yet) o Half of all known drugs work through GPCRs and their pathways  7 membrane spanning domains “serpentine receptors”  Trimeric GTP-binding proteins= G protein  Figure 15-31  Alpha binds GTP/GDP o Beta and gamma o Membrane bound b.c they possess a fatty acid attached, this is enough to make them a membrane bound intrinsic protein o Fatty acids are what attach them to the membrane  Many G-proteins with slightly different structures and are specific for their receptors (GPCRs) and targets  Figure 15-19  GTP proteins are different from G coupled proteins  Figure 15-32 Activation: receptor is GEF  Activate receptor--> conformational change  Receptor--> causes conformational change in G protein-->causing exchange of GDP for GTP-->activates G protein  One active receptor-->many G proteins  Alpha and or beta-gamma subunits activated o May or may not dissociate  Intestuitive targets=ion channels or enzymes  Alpha= GDT o GTP-->GDP inactivate o Trimeric re-rorms o Inactive receptor- maybe by phosphorylation Enzymes Make small intracellular mediators= second messengers Cyclic AMP  Found in all animal cells + prokaryotes  Made: adenylyl cyclase  Destroyed: cAMP phosphodiesterase  Adenylyl cyclase: activated by Gs= stimulatory  Increases cAMP production  Cholera toxin= inhibits o GTPase activity of alpha Gs o cAMP remains high o Figure 15-34 o Intestinal epithelial cells: high cAMP o Efflux of Cl- into gut o H2O in gut o Causes diarrhea of cholera  Table 15-1 in text  Many different tissues use cAMP o Many different
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