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dc.contributor.advisorCantley, Lewis
dc.contributor.authorWang, Diana
dc.date.accessioned2019-03-26T19:18:57Z
dc.date.available2020-07-16T06:00:37Z
dc.date.issued2020
dc.identifier.urihttps://hdl.handle.net/1813/64814
dc.description.abstractPhosphatidylinositol-4-phosphate-5-kinase (PIP5K) and phosphatidylinositol-5-phosphate-4-kinase (PIP4K) are two families of lipid kinases that catalyze production of phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2). The majority of cellular PI(4,5)P2 is produced by PIP5Ks, using PI(4)P as a substrate. In a non-canonical pathway, PIP4Ks catalyze the conversion of PI(5)P into PI(4,5)P2, but the importance of PIP4K has remained unclear. Unexpectedly, we find that PIP4K has a kinase independent role in regulating cellular PI(4,5)P2 levels. We demonstrate that PIP4Ks act as negative regulators of PIP5Ks and that depletion of PIP4K causes hyperactivation of PIP5Ks. Increased cellular PI(4,5)P2 generation by PIP5Ks promotes flux through the PI3K pathway, and these effects are reversed by reconstitution with kinase-dead PIP4K. This novel role for PIP4Ks provides an additional mechanism by which these kinases regulate cellular metabolism, which has the potential to be exploited by therapeutics.
dc.language.isoen_US
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectAkt
dc.subjectPhosphatidylinositol
dc.subjectPhosphoinositide
dc.subjectPI3K
dc.subjectPIP4K
dc.subjectPIP5K
dc.titlePip4K Has A Catalytic-Independent Role In Modulating Pip5K And The Pi3K Pathway
dc.typedissertation or thesis
thesis.degree.disciplineBiochemistry & Structural Biology
thesis.degree.grantorWeill Cornell Graduate School of Medical Sciences
thesis.degree.levelDoctor of Philosophy


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