Format

Send to

Choose Destination
Mol Cell. 2014 Mar 6;53(5):700-9. doi: 10.1016/j.molcel.2014.02.015.

SAICAR induces protein kinase activity of PKM2 that is necessary for sustained proliferative signaling of cancer cells.

Author information

1
Department of Biology, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218, USA.
2
Department of Biology, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218, USA. Electronic address: ylee99@jhu.edu.

Abstract

Abnormal metabolism and sustained proliferation are hallmarks of cancer. Pyruvate kinase M2 (PKM2) is a metabolic enzyme that plays important roles in both processes. Recently, PKM2 was shown to have protein kinase activity phosphorylating histone H3 and promoting cancer cell proliferation. However, the mechanism and extent of this protein kinase in cancer cells remain unclear. Here, we report that binding of succinyl-5-aminoimidazole-4-carboxamide-1-ribose-5'-phosphate (SAICAR), a metabolite abundant in proliferating cells, induces PKM2's protein kinase activity in vitro and in cells. Protein microarray experiments revealed that more than 100 human proteins, mostly protein kinases, are phosphorylated by PKM2-SAICAR. In particular, PKM2-SAICAR phosphorylates and activates Erk1/2, which in turn sensitizes PKM2 for SAICAR binding through phosphorylation. Additionally, PKM2-SAICAR was necessary to induce sustained Erk1/2 activation and mitogen-induced cell proliferation. Thus, the ligand-induced protein kinase activity from PKM2 is a mechanism that directly couples cell proliferation with intracellular metabolic status.

Comment in

PMID:
24606918
PMCID:
PMC4000728
DOI:
10.1016/j.molcel.2014.02.015
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center