期刊
JOURNAL OF BONE AND MINERAL RESEARCH
卷 15, 期 9, 页码 1716-1730出版社
AMER SOC BONE & MINERAL RES
DOI: 10.1359/jbmr.2000.15.9.1716
关键词
MC3T3-E1 osteoblast cells; proliferation; apoptosis; nucleus; phosphatidylinositol 3-kinase
Changes in the metabolism of nuclear inositides phosphorylated in the D3 position of the inositol ring, which may act as second messengers, mainly have been linked to cell differentiation. To clarify a possible role of this peculiar class of inositides also during cell proliferation and/or apoptosis, we have examined the issue of whether or not in the osteoblast-like clonal cell line MC3T3-E1 it may be observed an insulin-like growth factor-I (IGF-I)- and platelet-derived growth factor (PDGF)-dependent nuclear translocation of an active phosphatidylinositol 3-kinase (PI 3-K), We found that both the growth factors increased rapidly and transiently both the amount and the activity of immunoprecipitable nuclear PI 3-K. Intranuclear PI 3-K exhibited a massive tyrosine phosphorylation on the p85 regulatory subunit, Moreover, by means of coimmunoprecipitation experiments, we showed the presence, in isolated nuclei, of the p110 beta catalytic subunit of PI 3-K. Enzyme translocation was blocked by the specific PI 3-K inhibitor LY294002. In contrast, intranuclear translocation of PI 3-K did not occur in response to the proapoptotic cytokine tumor necrosis factor alpha (TNF-alpha), IGF-I was able to counteract the apoptotic stimulus of TNF-alpha and this was accompanied by the intranuclear translocation of PI 3-K. LY294002 inhibited both intranuclear translocation of PI 3-K and the rescuing effect of IGF-I, These findings strongly suggest that an important step in the signaling pathways that mediate both cell proliferation and survival is represented by the intranuclear translocation of PI 3-K.
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