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Cancer - Principles & Practice of Oncology
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Oncology.iso
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CHAP6
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F7.CAP
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1999-06-07
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FIGURE 6-7. Schematic illustration of two pathways which transduce
extracellular signals to the control of intracellular and intranuclear
events. EGF is illustrated as an example of a growth factor which
binds to its receptor and initiates a cascade of events, beginning
with the autophosphorylation of the receptor itself. The adaptor
protein, Grb2, then binds to the phosphorylated receptor, which then
binds to the guanine nucleotide releasing factor, Sos. This complex
leads to activation of Ras by exchanging GDP for GTP and the GTP-bound
active form of Ras binds to the serine/threonine kinase Raf. Raf
phosphorylates and activates MAPKK, which in turn phosphorylates and
activates MAPK. The targets phosphorylated by MAPK appear to be both
cytoplasmic and nuclear proteins, at least some of which can activate
transcription of certain gene products involved in cell proliferation.
The Jak/STAT pathway is illustrated here as being initiated by
interferon binding to its receptor, which leads to activation of
members of the Jak family of nonreceptor tyrosine kinases. These
kinases then phosphorylate members of the STAT family of transcription
factors on tyrosine residues, which translocate to the nucleus, bind
specific DNA sequences, and promote transcription. It also appears
that binding of certain growth factors to their receptors can also
activate the Jak kinases and that MAP kinase phosphorylation of serine
residues on STAT proteins enhances their transcriptional activity.