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Bos 18112009 1
Bos 18112009 1
Bos 18112009 1
Bos 18112009 1
Bos 18112009 1
Bos 18112009 1
Bos 18112009 1
Bos 18112009 1
Bos 18112009 1
Bos 18112009 1
Bos 18112009 1
Bos 18112009 1
Bos 18112009 1
Bos 18112009 1
Bos 18112009 1
Bos 18112009 1
Bos 18112009 1
Bos 18112009 1
Bos 18112009 1
Bos 18112009 1
Bos 18112009 1
Bos 18112009 1
Bos 18112009 1
Bos 18112009 1
Bos 18112009 1
Bos 18112009 1
Bos 18112009 1
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Bos 18112009 1

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  • 1.
  • 2. Principes om [Ca2+] laag te houden in de cel (10-3 vs 10-7)
    Plasma membraan:
    Na+-driven Ca2+-antiport
    Ca2+-ATPase
    Interne membranen
    ER: Ca2+-ATPase
    Calcium bindende eiwitten
    Mitochondrien: actieve import
  • 3. Calcium wave in fertilized egg
  • 4. Calmoduline: een veel gebruikt calcium "receptor"
  • 5. "Dual regulation" van CaCM (calmodulin) kinase
  • 6. Dual regulation of "multisubunit" phosphorylase kinase
    Complex bevat eigenlijk vier subunits van elk
  • 7.
  • 8. General structure Receptor tyrosine kinase
    Figure 5.9a The Biology of Cancer (© Garland Science 2007)
  • 9. Many different types of RTKs: different ligand binding sites
    Figure 5.10 The Biology of Cancer (© Garland Science 2007)
  • 10. Many different types of RTKs: different but overlapping intracellular docking domains
    Figure 6.9 The Biology of Cancer (© Garland Science 2007)
  • 11. 1. Ligand binding
    2. Dimerisatie
    3. Activatie kinase
    4. Kruisfosforylering
    General principle of activation
    Dimerisation + activation
  • 12. Sometimes the kinase is associated
  • 13. Tyrosine gefosforyleerde receptor fungeert als "docking site" voor signalerings enzymen
  • 14. Signaleringsroutes: vorming van eiwit complexen via specifieke eiwit-domeinen
  • 15. Adaptor eiwitten bevatten vaak meerdere “herkenningsdomeinen”
  • 16. Receptor tyrosine kinases maken vaak gebruik van specifieke membraan-gebonden "docking proteins"
  • 17. One of the effects of RTK activation:
    activation of the G-binding protein Ras
    1: RTK bindt complex van Grb2 en Sos
    2: Sos is guanine nucleotide exchange factor voor Ras
    3: GDP wordt uitgewisseld voor GTP
    Grb2
    Sos
  • 18. Ras, a molecular switch
    GDP
    GEF
    GTP
    Ras
    Ras
    Effector
    GAP
    Mutated in tumors
    vvvvvv
    GEF:
    guanine nucleotide exchange factor
    GAP:
    GTPase activating protein
  • 19. Mechanism of Ras activation by guanine nucleotide exchange factor
  • 20. Mechanism of Ras inactivation by
    GTPase activating protein
    Mechanisme van GAP geinduceerde hydrolyse
  • 21. Visualisation of Ras activation by FRET
    FRET
    (fluorescent resonance energy transfer)
    Mochizuli et al., Nature , 411 (2001) 1066
  • 22. Ras activates Raf-MEK-ERK pathway (a MAP kinase cascade
    Raf
    MEK:
    MAP-ERK kinase
    MEK
    ERK:
    extracellular signal-regulated kinase
    Also called: MAP kinase
    ERK
  • 23. Many stimuli can activate
    Ras by different mechanisms
  • 24. Cycl D1
    Ets
    ERK
    PLCe
    Endocytosis
    Cell cycle control
    MEK
    Rab5
    Raf1
    B-raf
    NFkB
    Rin
    RalBP
    “Exocist”
    Stat3
    RalGEF
    Ral
    JNK
    Jun
    PI-3K
    Cell cycle control
    Tiam
    PIP3
    AFX
    FKHR
    FKHR-L1
    p27
    p130
    PKB
    Rac
    PTEN
    Cytoskeleton
    GSK3
    Survival
    PDK
    Bad
    FasL
    Bim
    MnSOD
    eNOS
    Ras activates multiple pathways
    EGF
    PDGF
    LPA
    Insulin
    TCR
    Etc.
    Etc.
    Etc.
    Shc
    R
    Grb2
    Ras
    SOS
  • 25. PI-3 kinase phosphorylates PIP2
    Figure 6.16b The Biology of Cancer (© Garland Science 2007)
  • 26. One of the proteins is PKB (also known as Akt)
    Fosforylatie door PDK’s maakt PKB actief en vrij
    Figure 6.19a The Biology of Cancer (© Garland Science 2007)
  • 27. PI3,4,5P3: Translocatie van Protein Kinase B (PKB)
    en PDK1 (kinase)
    PDK1: Activatie van Protein Kinase B (PKB)

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