Building Blocks of Cells Part 2 Signal Transduction (Tyr Receptor) PDF 2024 Brunel University

Introduction to Medical Sciences 1 Building Blocks of Cells Part 2 Signal transduction (Tyr receptor) Copyright © Brunel University London v.3 2024. All rights reserved Building Blocks of Cells Dr Ricardo Carnicer Hijazo 2024 Version 3 Ricardo.CarnicerHijazo@brune...

Introduction to Medical Sciences 1 Building Blocks of Cells Part 2 Signal transduction (Tyr receptor) Copyright © Brunel University London v.3 2024. All rights reserved Building Blocks of Cells Dr Ricardo Carnicer Hijazo 2024 Version 3 [email protected] Copyright © Brunel University London v.3 2024. All rights reserved 5 Functions of Membrane Proteins 1. Signal 2. Transport 3. Intercellular Transduction Connections 4. Cell-Cell 5. Cell 6. Enzyme Recognition Attachment Activity Copyright © Brunel University London v.3 2024. All rights reserved 6 1. Signal transduction Ligand Receptor Signal transduction pathways Image by RCH. Content is available under CC BY-SA 3.0 RESPONSE Copyright © Brunel University London v.3 2024. All rights reserved 7 Cyclic-AMP cascade Low Glucose in blood! Glucagon Glucagon Receptor Adenylyl cyclase ATP Cyclic AMP Protein Kinase A Phosphorylation RESPONSE Glycogen Glucose cAMP: cyclic adenosine monophosphate Copyright © Brunel University London v.3 2024. All rights reserved 8 1. Signal transduction A) G protein-coupled receptors Cyclic AMP pathway Phosphatidylinositide pathway B) Receptor tyrosine kinases MAP Kinases pathway Phosphatidylinositide pathway Copyright © Brunel University London v.3 2024. All rights reserved 9 Receptor tyrosine kinases Receptor structure - N-terminal extracellular binding site Ligand binding for ligands. domain - One transmembrane helix. Plasma - C-terminal intracellular binding site membrane with tyrosine kinase activity. Tyrosine kinase domain Copyright © Brunel University London v.3 2024. All rights reserved 10 Receptor tyrosine kinases Receptor structure - N-terminal extracellular binding site Ligand binding for ligands. domain - One transmembrane helix. Plasma - C-terminal intracellular binding site membrane with tyrosine kinase activity. Tyrosine kinase domain Kinase activity: addition of a phosphate molecule. Copyright © Brunel University London v.3 2024. All rights reserved 11 Receptor tyrosine kinases Receptor structure - N-terminal extracellular binding site Ligand binding for ligands. domain - One transmembrane helix. Plasma - C-terminal intracellular binding site membrane with tyrosine kinase activity. Tyrosine kinase domain Tyrosine amino acid P Copyright © Brunel University London v.3 2024. All rights reserved 12 Receptor tyrosine kinases Receptor structure - N-terminal extracellular binding site Ligand binding for ligands. domain - One transmembrane helix. Plasma - C-terminal intracellular binding site membrane with tyrosine kinase activity. Tyrosine kinase domain Tyrosine amino acid Copyright © Brunel University London v.3 2024. All rights reserved 13 Receptor tyrosine kinases Receptor structure - N-terminal extracellular binding site Ligand binding for ligands. domain - One transmembrane helix. Plasma - C-terminal intracellular binding site membrane with tyrosine kinase activity. Tyrosine kinase domain Tyrosine amino acid 1 2 3 4 Copyright © Brunel University London v.3 2024. All rights reserved 14 Receptor tyrosine kinases Receptor structure - N-terminal extracellular binding site Ligand binding for ligands. domain - One Stop the transmembrane video and name helix. these Plasma - C-terminal intracellular binding membrane four main chemical groups in site the with tyrosine kinase activity. Tyrosine kinase amino acid. domain Tyrosine amino acid 1 2 3 4 Copyright © Brunel University London v.3 2024. All rights reserved 15 Receptor tyrosine kinases Receptor structure - N-terminal extracellular binding site Ligand binding for ligands. domain - One transmembrane helix. Plasma - C-terminal intracellular binding site membrane with tyrosine kinase activity. Tyrosine kinase domain 1- Amino Tyrosine amino acid 2- Carboxyl 3- Alpha carbon 4- Variable side chain Copyright © Brunel University London v.3 2024. All rights reserved 16 Receptor tyrosine kinases Receptor structure - N-terminal extracellular binding site Ligand binding for ligands. domain - One transmembrane helix. Plasma - C-terminal intracellular binding site membrane with tyrosine kinase activity. Tyrosine kinase domain Ligands - Growth factors. - Hormones. - Cytokines Copyright © Brunel University London v.3 2024. All rights reserved 17 Receptor tyrosine kinases Receptor structure - N-terminal extracellular binding site Ligand binding for ligands. domain - One transmembrane helix. Plasma - C-terminal intracellular binding site membrane with tyrosine kinase activity. Tyrosine kinase domain Functions - Proliferation, differentiation, growth, migration Copyright © Brunel University London v.3 2024. All rights reserved 18 Activation of Receptor tyrosine kinases 1 2 Growth 3 Growth factor factor Receptor P P 1 Inactive receptor Copyright © Brunel University London v.3 2024. All rights reserved 19 Activation of Receptor tyrosine kinases 1 2 Growth 3 Growth factor factor Receptor P P 1 Inactive receptor 2 Receptor dimerisation Copyright © Brunel University London v.3 2024. All rights reserved 20 Activation of Receptor tyrosine kinases 1 2 Growth 3 Growth factor factor Receptor P P 1 Inactive receptor 3 Auto-phosphorylation 2 Receptor dimerisation 4 Deactivation by phosphatases Copyright © Brunel University London v.3 2024. All rights reserved 21 Activation of Receptor tyrosine kinases 1 2 Growth 3 Growth factor factor Receptor P P 1 Inactive receptor 3 Auto-phosphorylation 2 Receptor dimerisation Copyright © Brunel University London v.3 2024. All rights reserved 22 Receptor tyrosine kinases signalling pathways 1. MAP kinase signal pathway 2. Phosphoinositide signal pathway Copyright © Brunel University London v.3 2024. All rights reserved 23 MAP kinase cascade Inflammatory cytokine Receptor GTP-binding protein (Ras) MAP kinases RESPONSE Phosphorylation GTP: guanosine triphosphate Inflammation and cell death MAP kinase: mitogen-activated protein kinase Image by RCH. Content is available under CC BY-SA 3.0 Copyright © Brunel University London v.3 2024. All rights reserved 24 Phosphoinositide cascade High blood glucose! Insulin Receptor PI3 kinase PIP2 IP3 AKT RESPONSE Phosphorylation PI3 kinase: phosphatidylinositide 3-kinase IP3: inositol triphosphate Glucose Glycogen AKT: serine/threonine kinase Image by RCH. Content is available under CC BY-SA 3.0 Copyright © Brunel University London v.3 2024. All rights reserved 25 Phosphoinositide cascade High blood glucose! Insulin Second messenger Receptor PI3 kinase PIP2 IP3 AKT RESPONSE Phosphorylation PI3 kinase: phosphatidylinositide 3-kinase IP3: inositol triphosphate Glucose Glycogen AKT: serine/threonine kinase Image by RCH. Content is available under CC BY-SA 3.0 Copyright © Brunel University London v.3 2024. All rights reserved 26 Receptor tyrosine kinases function - Cell growth and division - Motility - Differentiation - Metabolism Receptor tyrosine kinases in disease - Loss of control of cell growth (cancer) Copyright © Brunel University London v.3 2024. All rights reserved 27 Tyrosine kinase receptor (Video) https://www.youtube.com/watch?v=fqo7EYIh0XM Copyright © Brunel University London v.3 2024. All rights reserved 28 To contact me: [email protected] Copyright © Brunel University London v.3 2024. All rights reserved