Lack of Evidence for PKM2 Protein Kinase Activity
The role of pyruvate kinase M2 (PKM2) in cell proliferation is controversial. A unique function of PKM2 proposed to be important for the proliferation of some cancer cells involves the direct activity of this enzyme as a protein kinase; however, a detailed biochemical characterization of this activi...
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| Format: | Article |
| Language: | en_US |
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Elsevier
2016
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| Online Access: | http://hdl.handle.net/1721.1/105827 https://orcid.org/0000-0002-7702-5877 https://orcid.org/0000-0003-0130-3428 https://orcid.org/0000-0002-6702-4192 |
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| author | Hosios, Aaron Marc Fiske, Brian Prescott Gui, Dan Yi Vander Heiden, Matthew G. |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Hosios, Aaron Marc Fiske, Brian Prescott Gui, Dan Yi Vander Heiden, Matthew G. |
| author_sort | Hosios, Aaron Marc |
| collection | MIT |
| description | The role of pyruvate kinase M2 (PKM2) in cell proliferation is controversial. A unique function of PKM2 proposed to be important for the proliferation of some cancer cells involves the direct activity of this enzyme as a protein kinase; however, a detailed biochemical characterization of this activity is lacking. Using [32P]-phosphoenolpyruvate (PEP) we examine the direct substrates of PKM2 using recombinant enzyme and in vitro systems where PKM2 is genetically deleted. Labeling of some protein species from [32P]-PEP can be observed; however, most were dependent on the presence of ADP, and none were dependent on the presence of PKM2. In addition, we also failed to observe PKM2-dependent transfer of phosphate from ATP directly to protein. These findings argue against a role for PKM2 as a protein kinase. |
| first_indexed | 2024-09-23T14:04:21Z |
| format | Article |
| id | mit-1721.1/105827 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T14:04:21Z |
| publishDate | 2016 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/1058272022-10-01T19:00:50Z Lack of Evidence for PKM2 Protein Kinase Activity Hosios, Aaron Marc Fiske, Brian Prescott Gui, Dan Yi Vander Heiden, Matthew G. Massachusetts Institute of Technology. Department of Biology Koch Institute for Integrative Cancer Research at MIT Hosios, Aaron Marc Fiske, Brian Prescott Gui, Dan Yi Vander Heiden, Matthew G. The role of pyruvate kinase M2 (PKM2) in cell proliferation is controversial. A unique function of PKM2 proposed to be important for the proliferation of some cancer cells involves the direct activity of this enzyme as a protein kinase; however, a detailed biochemical characterization of this activity is lacking. Using [32P]-phosphoenolpyruvate (PEP) we examine the direct substrates of PKM2 using recombinant enzyme and in vitro systems where PKM2 is genetically deleted. Labeling of some protein species from [32P]-PEP can be observed; however, most were dependent on the presence of ADP, and none were dependent on the presence of PKM2. In addition, we also failed to observe PKM2-dependent transfer of phosphate from ATP directly to protein. These findings argue against a role for PKM2 as a protein kinase. Howard Hughes Medical Institute (International Student Research Fellowship) Vertex Pharmaceuticals Incorporated. Vertex Scholars Program Massachusetts Institute of Technology. Department of Biology (Grant T32GM007287) David H. Koch Institute for Integrative Cancer Research at MIT (Graduate Student Fellowship) National Cancer Institute (U.S.) (Grants R01CA168653 and P30CA14051) Burroughs Wellcome Fund 2016-12-15T15:42:40Z 2016-12-15T15:42:40Z 2015-08 2015-07 Article http://purl.org/eprint/type/JournalArticle 10972765 http://hdl.handle.net/1721.1/105827 Hosios, Aaron M. et al. “Lack of Evidence for PKM2 Protein Kinase Activity.” Molecular Cell 59.5 (2015): 850–857. https://orcid.org/0000-0002-7702-5877 https://orcid.org/0000-0003-0130-3428 https://orcid.org/0000-0002-6702-4192 en_US http://dx.doi.org/10.1016/j.molcel.2015.07.013 Molecular Cell Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier PMC |
| spellingShingle | Hosios, Aaron Marc Fiske, Brian Prescott Gui, Dan Yi Vander Heiden, Matthew G. Lack of Evidence for PKM2 Protein Kinase Activity |
| title | Lack of Evidence for PKM2 Protein Kinase Activity |
| title_full | Lack of Evidence for PKM2 Protein Kinase Activity |
| title_fullStr | Lack of Evidence for PKM2 Protein Kinase Activity |
| title_full_unstemmed | Lack of Evidence for PKM2 Protein Kinase Activity |
| title_short | Lack of Evidence for PKM2 Protein Kinase Activity |
| title_sort | lack of evidence for pkm2 protein kinase activity |
| url | http://hdl.handle.net/1721.1/105827 https://orcid.org/0000-0002-7702-5877 https://orcid.org/0000-0003-0130-3428 https://orcid.org/0000-0002-6702-4192 |
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