Protein Kinase Classification: Atypical/PKM2※ PKM2 family introduction Pyruvate kinase regulates the final rate-limiting step of glycolysis, which catalyzes the transfer of a phosphate group from phosphoenolpyruvate (PEP) to adenosine diphosphate (ADP), yielding one molecule of pyruvate and one molecule of adenosine triphosphate (ATP). PKM2 binds to the spindle checkpoint protein Bub3 during mitosis and phosphorylates Bub3 at Tyr207 (1). Using PEP as a phosphate donor, nuclear PKM2 can also phosphorylate histone H3 at Thr11 in nucleosomes associated with gene promoter regions (2). Notably, PKM2 binds directly and selectively to tyrosine (Tyr, Y)-phosphorylated peptides, and expression of the phosphotyrosine-binding form of PKM2 is required for the rapid growth of cancer cells (3).
Reference
1. Yang W, Xia Y, Hawke D, Li X, Liang J, Xing D, Aldape K, Hunter T, Yung WKA, Lu Z. (2014) PKM2 Phosphorylates Histone H3 and Promotes Gene Transcription and Tumorigenesis. Cell, 158(5), 1210. PMID: 28917293
2. Lu Z, Hunter T. (2018) Metabolic Kinases Moonlighting as Protein Kinases. Trends Biochem Sci, 43(4), 301-310. PMID: 29463470
3. Kaneko T, Joshi R, Li SS. (2012) Phosphotyrosine recognition domains: the typical, the atypical and the versatile. Cell Commun Signal, 10(1), 32. PMID: 23134684
Atypical PKM2 in eukaryotes:
1. Yang W, Xia Y, Hawke D, Li X, Liang J, Xing D, Aldape K, Hunter T, Yung WKA, Lu Z. (2014) PKM2 Phosphorylates Histone H3 and Promotes Gene Transcription and Tumorigenesis. Cell, 158(5), 1210. PMID: 28917293
2. Lu Z, Hunter T. (2018) Metabolic Kinases Moonlighting as Protein Kinases. Trends Biochem Sci, 43(4), 301-310. PMID: 29463470
3. Kaneko T, Joshi R, Li SS. (2012) Phosphotyrosine recognition domains: the typical, the atypical and the versatile. Cell Commun Signal, 10(1), 32. PMID: 23134684
Atypical PKM2 in eukaryotes: