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C8. Mitogen Activated Protein Kinases

  • Page ID
    5610
  •  

    It is often the case that occupied receptors activate protein kinases, which activate other protein kinases, which activate yet other protein kinases to produce phospho-proteins which may act as transcription factors. An example is the mitogen activated protein kinase (MAPK system). A mitogen is an external chemical signal that causes mitosis or cell division. Activated of transcription factors by their phosphorylation through a mitogen activated kinase is required. The sequence of events is:

    • binding of external signal to membrane receptor and activation of receptor kinase
    • phosphorylation of receptor kinase and interaction with an activator GTP binding protein like ras
    • binding of activated G-protein to and activation of a mitogen activated protein kinase kinase kinase (MAPKKK)
    • MKKK phosphorylates and activates another kinase, MAPKK
    • MKK phosphorylates and activates mitogen activated protein kinase, MAPK
    • MAPK phosphorylates inactive transcription factors (or other proteins) and activates them. Unfortunately (from a naming point of view) when the activated proteins are themselves protein kinase, they are called mitogen activated protein kinase activated protein kinases (MAPKAPK)

    There are seven types of MAPKs, four conventional and three atypical. Four typical ones are described in the table below. 

    Activator GTP binding protein Ras:GTP      
    MAPKKK or MAPK3 Raf-1A/B
    c-Mos
    MEKK1-4
    DLK
    MLK2
    MEKK1-4
    DLK
    MLK2
    MEKK2/3
    Tpl-2
    MAPKK or MAPK2 MEK1,2 MEK4,7 MEK3,6 MEK5
    MAPK or MAK ERK1,2 JNK1-3 p38 ERK5
    MAPKAPK RSK 1-4
    MNK2
    MSK 1,2
    MK2,3 MSK1,2
    MK2,3
    RSK1-4
    An eventual
    Protein Target
    c-Jun c-Jun    

    MAP Kinase System from Cell Signaling

    MAP Kinase System animation from Promega

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