Cell biology Lecture 6
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This document provides an overview of the topics covered in an advanced cell biology course, including cell signaling pathways. The course covers cell structures like the nucleus and membranes, as well as processes like transcription, splicing, trafficking and the cell cycle. It focuses on how cells use receptor proteins and second messengers to transduce chemical and physical stimuli into responses that regulate gene expression, metabolism, secretion and motility. Specific signaling pathways discussed include G protein-coupled receptors, receptor tyrosine kinases, cytokine receptors, MAP kinase pathways, insulin signaling, TGF-beta signaling, calcium signaling and visual transduction in vertebrates.
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Cell biology Lecture 6
- 1. Advanced Cell Biology 2014 1nd Semester Department of Animal Science Chungbuk National University 6th Lecture
- 2. 1st week : Introduction 3rd week :Research Strategies For Cell Biology 5nd week : Nucleus, Transcription and Splicing 7nd week : Membrane and Channel 9nd week : Membrane Trafficking 11nd week : Cell Signaling 13nd week : Cytoskeleton 15nd week : Cell Cycle
- 3. • Eukaryotic cells need to adapt to changing environmental conditions • Transducing chemical or physical stimuli -> activity • Short term responses mediates changes in – Metabolic activity – Secretion – Cell motility • Long Term responses mediates changes in - Gene Expression Why cell need Cell Signaling?
- 5. • Cell uses about 20 different families of receptor proteins to detect and respond to the different incoming chemical and physical stimuli Receptors
- 8. • GPCR : uses trimeric GTP-binding proteins to relay signals to effector protein insie cells • Mammals has ~2,000 different seven-helix receptors to discriminate odorants, light, amino acids, peptide, hormones, lipids. • S375 orphan receptors : Receptors with unknown ligands Seven-Helix Receptors
- 9. Ligands: alkaloids (opioids), biogenic amines (epinephrine), lipids (prostaglandins), neurotransmitters (acetylcholine, glutamate, dopamine), organic molecules (odorants), peptide hormones (glucagon, ACTH), proteins (parathyroid hormone, thrombin, interleukin- 8), rhodopsin (photoreceptor pigment activated by light). Many useful drugs.
- 19. Ligands : All ligands are proteins - Insulin - EGF - Platelet-derived growth factor (PDGF) - Fibroblast growth factor (FGF) Activation - Unbounded (Inactive) receptor diffuse in the membrane - Ligands bring together two receptor molecules - Activation of tyrosin kinase - transphosphorylation of kinase domains Receptor Tyrosin Kinase
- 20. Epidermal Growth Factor Receptor Kinase Effectors Phospholipase C gamma : bind P-tyr, produced IP3 and diacylgycerol GEF : binds P-tyr and activate Ras or Map Kinase
- 21. Cytokine Receptor associated with Cytoplasmic Tyrosin Kinase
- 25. Protein Phosphorylation Protein Kinase Protein Phosphatase Most common posttranslational modifications
- 26. Effects of Phosphorylation on Protein Structure and Function - Interference of substrate binding
- 28. Serine/Threonine Kinase and Tyrosine Kinase
- 29. Regulation of Protein Kinase • Activation by phosphorylation - Src-family tyrosine kinase - MAP kinase - cyclin-dependent kinase - calcium-depenent kinase • Inhibition by phosphorylation - Phosphorylation of Myosin-Light Chain Kinase by PKC : inhibit activity • Regulation of substrate binding - binding of regulatory subunit : inhibit substrate binding - autoinhibtion
- 30. Regulation of Protein Kinase • Targeting - PKA location was determined by RI and RII subunit = Kinase-anchoring proteins • PH Domain and lipid tag : target some kinase to lipid bilayer • Scaffolding Proteins : Cellular ‘Matchmaker’
- 32. Number of Protein Kinase Genes in Human/Mouse Genome - Serine/Threonine Kinase : 289 - Tyrosine Kinase : 123 ~= more than 500 Number of Protein Phosphatases - Serine/Threonine phosphatase : 18 - Tyrosine phosphatase : 40 Total Number of Protein Phosphtase : less than 60
- 33. Substrate Targeting Subunit of PP Protein Phosphatase 1 + Myosin Light Chain Kinase Targeting Subunits (MYPT1) Catalytic subunit of Protein Phosphatase relies on Targeting Subunit for substrate specifities
- 34. GTP binding protein (GTPase) Small GTPase Ras family Rho family : Rho, Rac, cdc42.. Rab family Ran
- 37. Linker between signaling molecules Small-conserved domains can be utilized as protein-protein linker between signaling proteins
- 40. Second Messengers in signaling pathway - Cyclic Nucleotide Activated by Adenylate/Guanylyl cyclase Deactivated by Phosphodiesterase
- 42. cAMP level up: 1. PKA activation 2. CDC25b phospho 3. Inactive CDC25b 4. Maintain GV Milirone dbcAMP
- 46. PKC family of Protein Kinases Activated by binding of lipid second messangers
- 49. Calcium (Ca2+) - ATP-driven calcium pump (SERCA) remove calcium from cytoplasm (0.1uM) - Activated Inositol Triphosphate Receptor release ER-calcium into cytoplasm
- 53. Calcium binding of calmodulin - Calcium binding of calmodulin change protein structure of calmodulin - Ca2+ bound calmodulin regulate various protein targets CaM Kinase (Calmodulin-dependent Protein Kinase)
- 54. Detection of Odors by the Olfactory System
- 57. Signaling Modulating gene expression