Cooper5e_Ch17

One of the major intracellular signaling pathways

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Unformatted text preview: ble for promoting cell survival is initiated by the enzyme PI 3-kinase, which is activated by either protein-tyrosine kinases or G protein-coupled receptors. PI 3-kinase phosphorylates the membrane phospholipid PIP2 to form PIP3, which activates the protein-serine/threonine kinase Akt (see Figures 15.30 and 15.31). Akt then phosphorylates a number of proteins that regulate apoptosis (Figure 17.11). One key substrate for Akt is the proapoptotic BH3only Bcl-2 family member called Bad. Phosphorylation of Bad by Akt creates a binding site for 14-3-3 chaperone proteins that sequester Bad in an inactive form, so phosphorylation of Bad by Akt inhibits apoptosis and promotes cell survival. Bad is similarly phosphorylated by protein kinases of other growth factor-induced signaling pathways, including the Ras/Raf/MEK/ERK pathway, so it serves as a convergent regulator of growth factor signaling in mediating cell survival. Other targets of Akt, including the FOXO transcription factors, also play key roles in cell survival. Phosphorylation of FOXO by Akt creates a binding site for...
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