Signal transduction pathways through small monomeric G proteins

Ras-controlled signal transduction the MAP kinase and the Ptdins 3-kinase pathways 

Having introduced Ras, the master switch of the MAP kinase (mitogen-activated protein kinase) signalling cascades, we are now ready to put the pieces of the puzzle together and sum up the essential features of a typical cellular signalling pathway, the Ras/MAP kinase 

The phosphorylation cascade consists of a sequence of kinases, starting with MAPKKKs, (MAP kinase kinase kinases) followed by MAPKKs (MAP kinase kinases), and ending with MAPKs (MAP kinases). 

Representative of upstream kinases which accept receptor signals are the Raf kinases. They are cytosolic Ser/Thr kinases. Raf kinase is recruited to the membrane and its activity is controlled by Ras. Raf phosphorylates and activates dual specificity, e.g. Ser/Thr-and Tyr-MAPKKs. The MAPKKs have a conserved serine/threonine phosphorylation site which is recognized and phosphorylated by Raf. 

Whereas, activation of MAPKKs and MAPKs (also known as extracellular signal-responsive kinases, ERKs), through traw -phosphorylation reactions is fairly well understood, activation of the upstream MAPKKKs, such as the Raf family of protein kinases, is more complicated. There are at least three human Raf kinases Raf-1, Raf-A, and Raf-B. The activation of the Raf kinase is controlled by Ras. This is a central point of control of the whole MAP kinase cascade. 

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Signal transduction pathways through small monomeric G proteins... 

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