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Serine is a natural ligand and allosteric activator of pyruvate kinase M2.

Chaneton B, Hillmann P, Zheng L, Martin ACL, Maddocks ODK, Chokkathukalam A, Coyle JE, Jankevics A, Holding FP, Vousden KH, Frezza C, O'Reilly M, Gottlieb E.

Nature. 2012 Nov 15;491(7424):458-462. doi: 10.1038/nature11540. Epub 2012 Oct 14. Erratum in: Nature. 2013 Apr 18;496(7445):386.


Pyruvate kinase M2 promotes de novo serine synthesis to sustain mTORC1 activity and cell proliferation.

Ye J, Mancuso A, Tong X, Ward PS, Fan J, Rabinowitz JD, Thompson CB.

Proc Natl Acad Sci U S A. 2012 May 1;109(18):6904-9. doi: 10.1073/pnas.1204176109. Epub 2012 Apr 16.


Pyruvate kinase M2 activators promote tetramer formation and suppress tumorigenesis.

Anastasiou D, Yu Y, Israelsen WJ, Jiang JK, Boxer MB, Hong BS, Tempel W, Dimov S, Shen M, Jha A, Yang H, Mattaini KR, Metallo CM, Fiske BP, Courtney KD, Malstrom S, Khan TM, Kung C, Skoumbourdis AP, Veith H, Southall N, Walsh MJ, Brimacombe KR, Leister W, Lunt SY, Johnson ZR, Yen KE, Kunii K, Davidson SM, Christofk HR, Austin CP, Inglese J, Harris MH, Asara JM, Stephanopoulos G, Salituro FG, Jin S, Dang L, Auld DS, Park HW, Cantley LC, Thomas CJ, Vander Heiden MG.

Nat Chem Biol. 2012 Oct;8(10):839-47. Erratum in: Nat Chem Biol. 2012 Dec;8(12):1008.


Insulin enhances metabolic capacities of cancer cells by dual regulation of glycolytic enzyme pyruvate kinase M2.

Iqbal MA, Siddiqui FA, Gupta V, Chattopadhyay S, Gopinath P, Kumar B, Manvati S, Chaman N, Bamezai RN.

Mol Cancer. 2013 Jul 9;12:72. doi: 10.1186/1476-4598-12-72.


Evidence for an alternative glycolytic pathway in rapidly proliferating cells.

Vander Heiden MG, Locasale JW, Swanson KD, Sharfi H, Heffron GJ, Amador-Noguez D, Christofk HR, Wagner G, Rabinowitz JD, Asara JM, Cantley LC.

Science. 2010 Sep 17;329(5998):1492-9. doi: 10.1126/science.1188015.


Death-associated protein kinase increases glycolytic rate through binding and activation of pyruvate kinase.

Mor I, Carlessi R, Ast T, Feinstein E, Kimchi A.

Oncogene. 2012 Feb 9;31(6):683-93. doi: 10.1038/onc.2011.264. Epub 2011 Jul 4.


Inhibition of pyruvate kinase M2 by reactive oxygen species contributes to the development of pulmonary arterial hypertension.

Guo D, Gu J, Jiang H, Ahmed A, Zhang Z, Gu Y.

J Mol Cell Cardiol. 2016 Feb;91:179-87. doi: 10.1016/j.yjmcc.2016.01.009. Epub 2016 Jan 13.


M2 isoform of pyruvate kinase is dispensable for tumor maintenance and growth.

Cortés-Cros M, Hemmerlin C, Ferretti S, Zhang J, Gounarides JS, Yin H, Muller A, Haberkorn A, Chene P, Sellers WR, Hofmann F.

Proc Natl Acad Sci U S A. 2013 Jan 8;110(2):489-94. doi: 10.1073/pnas.1212780110. Epub 2012 Dec 24.


Pyruvate kinase M2 expression, but not pyruvate kinase activity, is up-regulated in a grade-specific manner in human glioma.

Mukherjee J, Phillips JJ, Zheng S, Wiencke J, Ronen SM, Pieper RO.

PLoS One. 2013;8(2):e57610. doi: 10.1371/journal.pone.0057610. Epub 2013 Feb 25.


Estradiol-17β upregulates pyruvate kinase M2 expression to coactivate estrogen receptor-α and to integrate metabolic reprogramming with the mitogenic response in endometrial cells.

Salama SA, Mohammad MA, Diaz-Arrastia CR, Kamel MW, Kilic GS, Ndofor BT, Abdel-Baki MS, Theiler SK.

J Clin Endocrinol Metab. 2014 Oct;99(10):3790-9. doi: 10.1210/jc.2013-2639. Epub 2014 Jan 28.


A Novel Role for Pyruvate Kinase M2 as a Corepressor for P53 during the DNA Damage Response in Human Tumor Cells.

Xia L, Wang XR, Wang XL, Liu SH, Ding XW, Chen GQ, Lu Y.

J Biol Chem. 2016 Dec 9;291(50):26138-26150. Epub 2016 Nov 3.


2-Oxo-N-aryl-1,2,3,4-tetrahydroquinoline-6-sulfonamides as activators of the tumor cell specific M2 isoform of pyruvate kinase.

Walsh MJ, Brimacombe KR, Veith H, Bougie JM, Daniel T, Leister W, Cantley LC, Israelsen WJ, Vander Heiden MG, Shen M, Auld DS, Thomas CJ, Boxer MB.

Bioorg Med Chem Lett. 2011 Nov 1;21(21):6322-7. doi: 10.1016/j.bmcl.2011.08.114. Epub 2011 Sep 14.


Pyruvate kinase: Function, regulation and role in cancer.

Israelsen WJ, Vander Heiden MG.

Semin Cell Dev Biol. 2015 Jul;43:43-51. doi: 10.1016/j.semcdb.2015.08.004. Epub 2015 Aug 13. Review.


Cyclosporine A inhibits breast cancer cell growth by downregulating the expression of pyruvate kinase subtype M2.

Jiang K, He B, Lai L, Chen Q, Liu Y, Guo Q, Wang Q.

Int J Mol Med. 2012 Aug;30(2):302-8. doi: 10.3892/ijmm.2012.989. Epub 2012 May 9.


Resveratrol inhibits cancer cell metabolism by down regulating pyruvate kinase M2 via inhibition of mammalian target of rapamycin.

Iqbal MA, Bamezai RN.

PLoS One. 2012;7(5):e36764. doi: 10.1371/journal.pone.0036764. Epub 2012 May 4.


A novel pyruvate kinase M2 activator compound that suppresses lung cancer cell viability under hypoxia.

Kim DJ, Park YS, Kim ND, Min SH, You YM, Jung Y, Koo H, Noh H, Kim JA, Park KC, Yeom YI.

Mol Cells. 2015 Apr;38(4):373-9. doi: 10.14348/molcells.2015.2314. Epub 2015 Mar 26.


Evaluation of thieno[3,2-b]pyrrole[3,2-d]pyridazinones as activators of the tumor cell specific M2 isoform of pyruvate kinase.

Jiang JK, Boxer MB, Vander Heiden MG, Shen M, Skoumbourdis AP, Southall N, Veith H, Leister W, Austin CP, Park HW, Inglese J, Cantley LC, Auld DS, Thomas CJ.

Bioorg Med Chem Lett. 2010 Jun 1;20(11):3387-93. doi: 10.1016/j.bmcl.2010.04.015. Epub 2010 Apr 11.


Pyruvate kinase M2 regulates gene transcription by acting as a protein kinase.

Gao X, Wang H, Yang JJ, Liu X, Liu ZR.

Mol Cell. 2012 Mar 9;45(5):598-609. doi: 10.1016/j.molcel.2012.01.001. Epub 2012 Feb 2.


Inhibition of pyruvate kinase M2 by reactive oxygen species contributes to cellular antioxidant responses.

Anastasiou D, Poulogiannis G, Asara JM, Boxer MB, Jiang JK, Shen M, Bellinger G, Sasaki AT, Locasale JW, Auld DS, Thomas CJ, Vander Heiden MG, Cantley LC.

Science. 2011 Dec 2;334(6060):1278-83. doi: 10.1126/science.1211485. Epub 2011 Nov 3.


SAICAR stimulates pyruvate kinase isoform M2 and promotes cancer cell survival in glucose-limited conditions.

Keller KE, Tan IS, Lee YS.

Science. 2012 Nov 23;338(6110):1069-72. doi: 10.1126/science.1224409. Epub 2012 Oct 18.

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