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G-Protein Coupled Receptors (Cont'd)

by: Sampath Choppara

G-Protein Coupled Receptors (Cont'd) MOLGEN 5607 - 0010

Marketplace > Ohio State University > Biochemistry > MOLGEN 5607 - 0010 > G Protein Coupled Receptors Cont d
Sampath Choppara
Cell Biology
Iris Meier,Paul Herman

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About this Document

Everything we've covered in class upto Oct. 7
Cell Biology
Iris Meier,Paul Herman
Class Notes
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This 3 page Class Notes was uploaded by Sampath Choppara on Tuesday October 20, 2015. The Class Notes belongs to MOLGEN 5607 - 0010 at Ohio State University taught by Iris Meier,Paul Herman in Fall 2015. Since its upload, it has received 122 views. For similar materials see Cell Biology in Biochemistry at Ohio State University.

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Date Created: 10/20/15
Chapter 15 Post Midterm Part 11 Tuesday October 13 2015 954 AM I G PROTElN COUPLED RECEPTORS CONT39D a G Protein signaling via Phospholipids i Phospholipase C B membrane bound enzyme activated by G proteins and GPCR l Acts on phosphatidylinositol 45 Bisphosphate PI45 P2 2 via inositol phospholipid signaling pathway involving Gq 3 Ultimate goalactivation of Protein Kinase C GPCR activates Gq protein as any other Receptor G Protein interaction Gq activates Phospholipase C B which cleaves PI 45 P2 into 145 Trisphosphate 1P3 and Diacylglycerol IP3 diffuses into cytosol Diacylglycerol remains attached to plasma membrane IP3 diffuses into cytosol and opens Ca2 channels in the ER membrane dramatic increase in Ca2 Increase in cytosolic Ca2 alters Protein Kinase C PKC so it relocates from cytosol to plasma membrane PKC is activated by combination of Ca2 diacylglycerol and phosphatidylserine Active PKC can now phosphorylate target proteins 0 U 9 0 2i 39 39 a v 39 o O o 0 0 o n O Q Q93 GatedCrZ Channels m 39 o u Pilmmunw ER Membrane Studysoup notes Page 1 b Calcium is a ubiquitous intracellular mediator i Critical to maintain a low Ca2 so that extracellular signals can increase it to activate Ca2 responsive proteins in cells ii Mechanisms are in place to keep Ca2 low in cytoplasm Ca2 Plasma Membrane Pumps Active transport to pump Ca2 out of cell NaCa2 exchanger and ATP driven pumps Ca2 binding molecules to decrease concentration of free Ca2 Ca2 Pumps on ER and Mitochondrial membranes active transport to pump Ca2 into organelles ATP Driven iii Calmodulin calcium binding protein that helps relay cytosolic Ca2 signal 1 Contains four high affinity Ca2 binding sites 2 Activated by Ca3 binding leading to a conformation change 3 Displays no enzymatic activity by itself but acts by binding to and activating other proteins iv Ca2Calmodulin dependent kinases mediate effects of Ca2 via phosphorylation Calmodulin Ca2 1 What we39re looking at gt CAM Kinase ll 39 1 Structure 12 subunits 6 kinase domains pink and 6 39 hub domains purple 2 Molecular memory ability to remain active even CalmolduilinCa2 after signal has decayed signalcalmodulin complex binds to Ca2 Calmodulin complex hl regulatory segment and r 7 kinase domain NOT t Compact regulatory V inhibited segment not available c B Vex a When inactive protein is CBS5113161 kinase d Tb domain popped out in ynamic equi 1 rium L regulatory subunit 7 7 between compact state 7 available and accessible state When the adjacent kinase domain pops out 7 i A V V l 39 r it will also become not J amp inhibited by calmodulin 7 r 3 Autophosphorylation occurs the two kinases phosphorylate each a r a a gt7 other and activate the a 39 39 enzyme Enzyme inactivated by m V protein phosphatase II A 7 r39 7 rl Enzyme remains active independent of calmodulin and Ca2 a 1 because of autophosphorylation Studysoup notes Page 2 II Target Cell adaption a Desensitization occurs because of prolonged exposure b Adaption can occur in various ways i Receptor sequestration l Receptors temporarily moved to interior of cell via endocytosis ii Receptor down regulation 1 Receptors destroyed with lysosomes after endocytosis iii Receptor Inactivation 1 Receptor altered to no longer interact with protein Lu iv Inactivation of signaling proteins 1 Inactivation of signaling protein v Production of inhibiting protein V c Desensitization of GPCR depends on phosphorylation via GPCR kinases i Kinases activated by activated receptor ii Once phosphorylated GPCR binds to arrestin family proteins 1 Now activated receptor can39t interact with G protein 2 Serves as adaptor protein for coat recruitment and endocytosis Studysoup notes Page 3


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