title: The Warburg Effect Mediator Pyruvate Kinase M2 Expression and Regulation in the Retina.
abstract: The tumor form of pyruvate kinase M2 (PKM2) undergoes tyrosine phosphorylation and gives rise to the Warburg effect. The Warburg effect defines a pro-oncogenic metabolism switch such that cancer cells take up more glucose than normal tissue and favor incomplete oxidation of glucose, even in the presence of oxygen. Retinal photoreceptors are highly metabolic and their energy consumption is equivalent to that of a multiplying tumor cell. In the present study, we found that PKM2 is the predominant isoform in both rod- and cone-dominant retina, and that it undergoes a light-dependent tyrosine phosphorylation. We also discovered that PKM2 phosphorylation is signaled through photobleaching of rhodopsin. Our findings suggest that phosphoinositide 3-kinase activation promotes PKM2 phosphorylation. Light and tyrosine phosphorylation appear to regulate PKM2 to provide a metabolic advantage to photoreceptor cells, thereby promoting cell survival.
authors.affiliation: Department of Ophthalmology, University of Oklahoma Health Sciences Center, 608 Stanton L. Young Blvd, Oklahoma City, OK 73104, USA.|Department of Physiology, University of Oklahoma Health Sciences Center, 940 Stanton L. Young Blvd, Oklahoma City, OK 73104, USA.|Department of Cell Biology, University of Oklahoma Health Sciences Center, 940 Stanton L. Young Blvd, Oklahoma City, OK 73104, USA.|Dean McGee Eye Institute, 608 Stanton L. Young Blvd, Oklahoma City, OK 73104, USA.|Oklahoma Center for Neuroscience, 975 N.E. 10th street, Oklahoma City, OK 73104,USA.
authors.forename: Raju V S
authors.initials: RV
authors.lastname: Rajala
authors.affiliation: Department of Ophthalmology, University of Oklahoma Health Sciences Center, 608 Stanton L. Young Blvd, Oklahoma City, OK 73104, USA.|Dean McGee Eye Institute, 608 Stanton L. Young Blvd, Oklahoma City, OK 73104, USA.
authors.forename: Ammaji
authors.initials: A
authors.lastname: Rajala
authors.affiliation: Department of Ophthalmology, University of Oklahoma Health Sciences Center, 608 Stanton L. Young Blvd, Oklahoma City, OK 73104, USA.|Dean McGee Eye Institute, 608 Stanton L. Young Blvd, Oklahoma City, OK 73104, USA.|Oklahoma Center for Neuroscience, 975 N.E. 10th street, Oklahoma City, OK 73104,USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Kooker
authors.affiliation: Department of Ophthalmology, University of Oklahoma Health Sciences Center, 608 Stanton L. Young Blvd, Oklahoma City, OK 73104, USA.|Dean McGee Eye Institute, 608 Stanton L. Young Blvd, Oklahoma City, OK 73104, USA.
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Ophthalmology, University of Oklahoma Health Sciences Center, 608 Stanton L. Young Blvd, Oklahoma City, OK 73104, USA.|Department of Cell Biology, University of Oklahoma Health Sciences Center, 940 Stanton L. Young Blvd, Oklahoma City, OK 73104, USA.|Dean McGee Eye Institute, 608 Stanton L. Young Blvd, Oklahoma City, OK 73104, USA.|Oklahoma Center for Neuroscience, 975 N.E. 10th street, Oklahoma City, OK 73104,USA.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Anderson
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000502:physiology; D005947:Glucose / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000502:physiology; D011770:Pyruvate Kinase / Q000378:metabolism*; D012160:Retina / Q000378:metabolism*
chemical_list: D008565:Membrane Proteins; D019869:Phosphatidylinositol 3-Kinases; D011770:Pyruvate Kinase; D005947:Glucose