Regulation of cell proliferation by interleukin-3-induced nuclear translocation of pyruvate kinase.
Extracellular signaling molecules bound to cell surface receptors can regulate nuclear function with consequences for cell proliferation, differentiation, and function. To regulate nuclear function, signals must be transduced across the nuclear envelope to propagate the signal from the cytoplasm to the nucleus. Therefore, many signaling responses induce the nuclear translocation of transcription factors, kinases, and others. By using inducible translocation trap, a reporter gene-based system to detect inducible nuclear translocation, we found that the M2 isoform of pyruvate kinase, a key enzyme in glycolysis, translocates into the nucleus by interleukin-3, but not by epidermal growth factor, stimulation. The C domain of the M2 isoform of pyruvate kinase was sufficient for interleukin-3-induced nuclear translocation. Interleukin-3-induced nuclear translocation of the M2 isoform of pyruvate kinase was dependent on the activation of Jak2. Overexpression of the M2 isoform of pyruvate kinase protein fused with a nuclear localization signal enhanced cell proliferation in the absence of interleukin-3, suggesting that the nuclear pyruvate kinase plays an important role in cell proliferation.
Hoshino
Akemi
A
Department of Pathology, New York University School of Medicine, New York, New York 10016, USA.
Hirst
John A
JA
Fujii
Hodaka
H
D021581:Active Transport, Cell Nucleus; D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation; D004789:Enzyme Activation; D006801:Humans; D007377:Interleukin-3 / Q000378:metabolism*; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D053614:Janus Kinase 2 / Q000378:metabolism; D051379:Mice; D019913:Nuclear Localization Signals / Q000235:genetics / Q000378:metabolism; D011770:Pyruvate Kinase / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
D007377:Interleukin-3; D007527:Isoenzymes; D019913:Nuclear Localization Signals; D011993:Recombinant Fusion Proteins; D011770:Pyruvate Kinase; D053614:Janus Kinase 2