Advanced Cell Biology
2014 1nd Semester
Department of Animal Science
Chungbuk National University
6th Lecture
1st week : Introduction
3rd week :Research Strategies For Cell Biology
5nd week : Nucleus, Transcription and Splicing
7nd ...
• Eukaryotic cells need to adapt to changing
environmental conditions
• Transducing chemical or physical stimuli ->
activi...
• Cell uses about 20 different families of
receptor proteins to detect and respond to
the different incoming chemical and ...
• GPCR : uses trimeric GTP-binding proteins to
relay signals to effector protein insie cells
• Mammals has ~2,000 differen...
Ligands: alkaloids (opioids), biogenic amines
(epinephrine), lipids (prostaglandins),
neurotransmitters (acetylcholine, gl...
Receptor Tyrosin Kinase
Ligands : All ligands are proteins
- Insulin
- EGF
- Platelet-derived growth factor (PDGF)
- Fibroblast growth factor (FGF...
Epidermal Growth Factor Receptor Kinase
Effectors
Phospholipase C gamma : bind P-tyr, produced IP3 and diacylgycerol
GEF :...
Cytokine Receptor associated with Cytoplasmic Tyrosin Kinase
Receptor Serine/Threonine Kinase
Protein Phosphorylation
Protein Kinase
Protein Phosphatase
Most common posttranslational modifications
Effects of Phosphorylation on Protein Structure and Function
- Interference of substrate binding
Serine/Threonine Kinase and Tyrosine Kinase
Regulation of Protein Kinase
• Activation by phosphorylation
- Src-family tyrosine kinase
- MAP kinase
- cyclin-dependent ...
Regulation of Protein Kinase
• Targeting
- PKA location was determined by RI and RII subunit
= Kinase-anchoring proteins
•...
Protein Phosphatases
Number of Protein Kinase Genes in Human/Mouse Genome
- Serine/Threonine Kinase : 289
- Tyrosine Kinase : 123
~= more than ...
Substrate Targeting Subunit of PP
Protein Phosphatase 1 + Myosin Light Chain Kinase Targeting Subunits (MYPT1)
Catalytic s...
GTP binding protein (GTPase)
Small GTPase
Ras family
Rho family : Rho, Rac, cdc42..
Rab family
Ran
Trimeric G-Proteins
Linker between signaling molecules
Small-conserved domains can be utilized as protein-protein linker between signaling pro...
Second Messengers in signaling pathway
- Cyclic Nucleotide
Activated by
Adenylate/Guanylyl cyclase
Deactivated by
Phosphod...
Adenylate cyclase
cAMP level up:
1. PKA activation
2. CDC25b phospho
3. Inactive CDC25b
4. Maintain GV
Milirone
dbcAMP
Lipid Second Messangers
PKC family of Protein Kinases
Activated by binding of lipid second messangers
Phosphatidylinositol metabolism
Calcium (Ca2+)
- ATP-driven calcium pump (SERCA) remove calcium from cytoplasm (0.1uM)
- Activated Inositol Triphosphate R...
Calcium binding of calmodulin
- Calcium binding of calmodulin change protein structure of calmodulin
- Ca2+ bound calmodul...
Detection of Odors by the Olfactory System
Vertebrate Visual Transduction
B-Adrenergic signaling
Signaling Modulating gene expression
MAP Kinase Pathways
Insulin signaling Pathways
TGF-beta signaling Pathways
Cell biology Lecture 6
Cell biology Lecture 6
Cell biology Lecture 6
Cell biology Lecture 6
Cell biology Lecture 6
Cell biology Lecture 6
Cell biology Lecture 6
Cell biology Lecture 6
Cell biology Lecture 6
Cell biology Lecture 6
Cell biology Lecture 6
Cell biology Lecture 6
Cell biology Lecture 6
Cell biology Lecture 6
Cell biology Lecture 6
Cell biology Lecture 6
Cell biology Lecture 6
Cell biology Lecture 6
Cell biology Lecture 6
Cell biology Lecture 6
Cell biology Lecture 6
Cell biology Lecture 6
Cell biology Lecture 6
Cell biology Lecture 6
Cell biology Lecture 6
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Cell biology Lecture 6

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Cell biology Lecture 6

  1. 1. Advanced Cell Biology 2014 1nd Semester Department of Animal Science Chungbuk National University 6th Lecture
  2. 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. 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?
  4. 4. • Cell uses about 20 different families of receptor proteins to detect and respond to the different incoming chemical and physical stimuli Receptors
  5. 5. • 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
  6. 6. 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.
  7. 7. Receptor Tyrosin Kinase
  8. 8. 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
  9. 9. 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
  10. 10. Cytokine Receptor associated with Cytoplasmic Tyrosin Kinase
  11. 11. Receptor Serine/Threonine Kinase
  12. 12. Protein Phosphorylation Protein Kinase Protein Phosphatase Most common posttranslational modifications
  13. 13. Effects of Phosphorylation on Protein Structure and Function - Interference of substrate binding
  14. 14. Serine/Threonine Kinase and Tyrosine Kinase
  15. 15. 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
  16. 16. 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’
  17. 17. Protein Phosphatases
  18. 18. 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
  19. 19. 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
  20. 20. GTP binding protein (GTPase) Small GTPase Ras family Rho family : Rho, Rac, cdc42.. Rab family Ran
  21. 21. Trimeric G-Proteins
  22. 22. Linker between signaling molecules Small-conserved domains can be utilized as protein-protein linker between signaling proteins
  23. 23. Second Messengers in signaling pathway - Cyclic Nucleotide Activated by Adenylate/Guanylyl cyclase Deactivated by Phosphodiesterase
  24. 24. Adenylate cyclase
  25. 25. cAMP level up: 1. PKA activation 2. CDC25b phospho 3. Inactive CDC25b 4. Maintain GV Milirone dbcAMP
  26. 26. Lipid Second Messangers
  27. 27. PKC family of Protein Kinases Activated by binding of lipid second messangers
  28. 28. Phosphatidylinositol metabolism
  29. 29. Calcium (Ca2+) - ATP-driven calcium pump (SERCA) remove calcium from cytoplasm (0.1uM) - Activated Inositol Triphosphate Receptor release ER-calcium into cytoplasm
  30. 30. 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)
  31. 31. Detection of Odors by the Olfactory System
  32. 32. Vertebrate Visual Transduction
  33. 33. B-Adrenergic signaling
  34. 34. Signaling Modulating gene expression
  35. 35. MAP Kinase Pathways
  36. 36. Insulin signaling Pathways
  37. 37. TGF-beta signaling Pathways

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