Sandbox Reserved 822: Difference between revisions
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Once activated by growth factors, various local responses, such as cell growth, cell survival and cell movement are regulated by the highly conserved PDK1 pathway. | Once activated by growth factors, various local responses, such as cell growth, cell survival and cell movement are regulated by the highly conserved PDK1 pathway. | ||
Therefore PDK1 binds to the lipid products of [[PI3K]], PtdIns(3,4,5)P<sub>3</sub> and PtdIns(3,4)P<sub>2</sub> (see 'Ligand Interaction'). Once localized to the plasma membrane PDK1 can phosphorylate PKB/Akt and thereby activate [http://en.wikipedia.org/wiki/Mammalian_target_of_rapamycin mTOR], which plays a major role in ageing mechanisms and Alzheimer’s disease. Other tumor supressors such as the phosphatidylinositol 3′-phosphatase [[PTEN]] act to down-regulate signaling from PI3K to PDK1 and PKB as well. <ref>Hemmings, Brian A., and David F. Restuccia. "PI3K-PKB/Akt Pathway." Cold Spring Harbor Perspectives in Biology 4.9 (2012) [http://cshperspectives.cshlp.org/content/4/9/a011189.full DOI:10.1101/cshperspect.a011189]</ref> | Therefore PDK1 binds to the lipid products of [[PI3K]], PtdIns(3,4,5)P<sub>3</sub> and PtdIns(3,4)P<sub>2</sub> (see ''''Ligand Interaction''''). Once localized to the plasma membrane PDK1 can phosphorylate PKB/Akt and thereby activate [http://en.wikipedia.org/wiki/Mammalian_target_of_rapamycin mTOR], which plays a major role in ageing mechanisms and Alzheimer’s disease. Other tumor supressors such as the phosphatidylinositol 3′-phosphatase [[PTEN]] act to down-regulate signaling from PI3K to PDK1 and PKB as well. <ref>Hemmings, Brian A., and David F. Restuccia. "PI3K-PKB/Akt Pathway." Cold Spring Harbor Perspectives in Biology 4.9 (2012) [http://cshperspectives.cshlp.org/content/4/9/a011189.full DOI:10.1101/cshperspect.a011189]</ref> | ||
Some other substrates of PDK1 are usually activated when the lipid-binding function of the protein is inhibited. Hence, not all PDK1 mediated reactions depend necessarily on the PH domain of PDK1. <ref>Scheid, Michael P., Michael Parsons, and James R. Woodgett. "Phosphoinositide-dependent phosphorylation of PDK1 regulates nuclear translocation." Molecular and cellular biology 25.6 (2005): 2347-2363. [http://mcb.asm.org/content/25/6/2347.full DOI:10.1128/MCB.25.6.2347-2363.2005]</ref> | Some other substrates of PDK1 are usually activated when the lipid-binding function of the protein is inhibited. Hence, not all PDK1 mediated reactions depend necessarily on the PH domain of PDK1. <ref>Scheid, Michael P., Michael Parsons, and James R. Woodgett. "Phosphoinositide-dependent phosphorylation of PDK1 regulates nuclear translocation." Molecular and cellular biology 25.6 (2005): 2347-2363. [http://mcb.asm.org/content/25/6/2347.full DOI:10.1128/MCB.25.6.2347-2363.2005]</ref> | ||