Nuclear localization of phospholipase D1 mediates the activation of nuclear protein kinase C(alpha) and extracellular signal-regulated kinase signaling pathways.
Recent studies highlight the existence of a nuclear lipid metabolism related to cellular proliferation. However, the importance of nuclear phosphatidylcholine (PC) metabolism is poorly understood. Therefore, we were interested in nuclear PC as a source of second messengers and, particularly, nuclear localization of PC-specific phospholipase D (PLD). In the present study we have identified the nuclear localization sequence (NLS) of PLD1 whose mutation abolished its nuclear import. Recently, we reported that caspase-mediated cleavage of PLD1 generates the N-terminal fragment (NF-PLD1) and C-terminal fragment (CF-PLD1). Here we show that CF-PLD1 but not NF-PLD1, is exclusively imported into the nucleus via its functional NLS, whereas only some portions of intact PLD1 were localized into the nucleus. The NLS of intact PLD1 or CF-PLD1 is required for interaction with importin-β, which is known to mediate nuclear import. The amount of intact PLD1 or CF-PLD1 translocated into nucleus is correlated with its binding affinity with importin-β. Ultimately, nuclear localization of intact PLD1 but not CF-PLD1 mediates the activation of nuclear protein kinase Cα and extracellular signal-regulated kinase signaling pathways. Taken together, we propose that nuclear localization of PLD1 via the NLS and its interaction with importin-β may provide new insights on the functional role of nuclear PLD1 signaling.
Department of Molecular Biology, College of Natural Science, Pusan National University, Busan 609-735, Korea.
Young Hoon
YH
Jang
Do Sik
do S
Min
D021581:Active Transport, Cell Nucleus / Q000502:physiology; D002467:Cell Nucleus / Q000201:enzymology* / Q000235:genetics; D004789:Enzyme Activation / Q000502:physiology; D057809:HEK293 Cells; D006801:Humans; D019913:Nuclear Localization Signals / Q000235:genetics / Q000378:metabolism*; D010739:Phospholipase D / Q000235:genetics / Q000378:metabolism*; D051571:Protein Kinase C-alpha / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D015398:Signal Transduction / Q000502:physiology*; D028961:beta Karyopherins / Q000235:genetics / Q000378:metabolism
D019913:Nuclear Localization Signals; D028961:beta Karyopherins; D051571:Protein Kinase C-alpha; D010739:Phospholipase D; C106801:phospholipase D1