Pyruvate kinase M2 is a phosphotyrosine-binding protein

By H. Christofk, M. V. Vander Heiden, Ning Wu, J. Asara, Lewis C. Cantley. Nature, 2008

1,008 citations recorded by the source corpus.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/c8e1d999171f446434bef4b2ab03cb4e59e8546d

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cancer Research

1. M. V. Vander Heiden
2. C. V. Dang
3. Ralph J. Deberardinis
4. Navdeep S. Chandel
5. Craig B. Thompson
6. Sophia Y. Lunt
7. David M. Sabatini
8. Guido Kroemer

In Molecular Biology

1. David M. Sabatini
2. Ralph J. Deberardinis
3. M. V. Vander Heiden
4. Navdeep S. Chandel
5. C. V. Dang
6. Craig B. Thompson
7. Guido Kroemer
8. J. Cantor

Citations in the corpus

• Nuclear PKM2 regulates β-catenin transactivation upon EGFR activation (2011, background): “PKM2 binds to tyrosine-phosphorylated peptides, and expression of the phosphotyrosine-binding form is required for cancer cell growt”
• Signal transduction in cancer. (2015, positive): “PKM1 remains active undermost physiological conditions, but PKM2 can be turned off by signaling via tyrosine kinases, including the upstream RTKs in the Ras-ERK and PI3K-Akt pathways (Christofk et al. 2008; Hitosugi et al. 2009) and reactive oxygen species (ROS) (Anastasiou et al. 2011).”
• PKM2 Phosphorylates Histone H3 and Promotes Gene Transcription and Tumorigenesis (2012, neutral): “This phosphorylation is required for the dissociation of HDAC3 from the CCND1 and MYC promoter regions and subsequent acetylation of histone H3 at K9.”
• Mitochondrial reactive oxygen species and cancer (2014, background): “In contrast to its constitutively active splice isoform PKM1, PKM2 is preferentially expressed in cancer cells and is unique due to its ability to be inhibited by a variety of stimuli [65,66].”
• Targeting mitochondrial glutaminase activity inhibits oncogenic transformation (2010, positive): “…and cellular metabolism in the development of cancer, and in particular, the early observations that tumor cells exhibit elevated glycolytic activity (i.e., the ‘‘War- burg effect’’) (Warburg, 1956), are receiving renewed attention (DeBerardinis et al., 2007; Christofk et al., 2008a, 2008b).”
• Tyrosine Phosphorylation Inhibits PKM2 to Promote the Warburg Effect and Tumor Growth (2009, background): “5) or PKM1 (8) effectively attenuates cancer cell proliferation in vitro and in vivo, PKM2 may serve as an interesting therapeutic target in cancer treatment, such that either inhibition or activation of PKM2 may affect cancer cell metabolism and cause tumor regression.”
• Aerobic glycolysis: meeting the metabolic requirements of cell proliferation. (2011, positive): “The M2 isoform can also be inhibited as a consequence of tyrosine kinase signaling in tumor cells (Christofk et al 2008b).”
• Tumor glycolysis as a target for cancer therapy: progress and prospects (2013, background): “PK-M2 acts as a kinase and phosphorylates histone H3 to favor tumorigenesis [54], as a nuclear protein it transactivates β-catenin [55], and as a phosphotyrosine binding protein it interacts with other proteins as well [56].”
• Regulation of cancer cell metabolism (2011, background): “Furthermore, it was discovered that although PKM1 could efficiently promote glycolysis and rapid energy generation, PKM2 is characteristically found in an inactive state and is ineffective at promoting glycolysi”
• Targeting cancer metabolism: a therapeutic window opens (2011, background): “PKM1 is a constitutively active enzyme, whereas PKM2 is unique among pyruvate kinase isoforms in that its enzyme activity is inhibited following its binding to tyrosine-phosphorylated proteins downstream of cellular growth signal”
• Tumor cell metabolism: cancer's Achilles' heel. (2008, background): “TAMs facilitate angiogenesis, promote tumor cell migration, and exert local immunosuppressive effects (Condeelis and Pollard, 2006).”