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dc.creatorValentinis, Barbara
dc.creatorNavarro, Magali
dc.creatorZanocco-Marani, Tommaso
dc.creatorEdmonds, Pamela
dc.creatorMcCormick, Jason
dc.creatorMorrione, Andrea
dc.creatorSacchi, Ada
dc.creatorRomano, Gaetano
dc.creatorReiss, Krzysztof
dc.creatorBaserga, Renato
dc.identifier.citationBarbara Valentinis, Magali Navarro, Tommaso Zanocco-Marani, Pamela Edmonds, Jason McCormick, Andrea Morrione, Ada Sacchi, Gaetano Romano, Krzysztof Reiss, Renato Baserga, Insulin Receptor Substrate-1, p70S6K, and Cell Size in Transformation and Differentiation of Hemopoietic Cells*, Journal of Biological Chemistry, Volume 275, Issue 33, 2000, Pages 25451-25459, ISSN 0021-9258,
dc.description.abstractAfter an initial burst of cell proliferation, the type 1 insulin-like growth factor receptor (IGF-IR) induces granulocytic differentiation of 32D IGF-IR cells, an interleukin-3-dependent murine hemopoietic cell line devoid of insulin receptor substrate-1 (IRS-1). The combined expression of the IGF-IR and IRS-1 (32D IGF-IR/IRS-1 cells) inhibits IGF-I-mediated differentiation, and causes malignant transformation of 32D cells. Because of the role of IRS-1 in changing the fate of 32D IGF-IR cells from differentiation (and subsequent cell death) to malignant transformation, we have looked for differences in IGF-IR signaling between 32D IGF-IR and 32D IGF-IR/IRS-1 cells. In this report, we have focused on p70S6K, which is activated by the IRS-1 pathway. We find that the ectopic expression of IRS-1 and the inhibition of differentiation correlated with a sustained activation of p70S6K and an increase in cell size. Phosphorylationin vivo of threonine 389 and, to a lesser extent, of threonine 421/serine 424 of p70S6K seemed to be a requirement for inhibition of differentiation. A role of IRS-1 and p70S6K in the alternative between transformation or differentiation of 32D IGF-IR cells was confirmed by findings that inhibition of p70S6K activation or IRS-1 signaling, by rapamycin or okadaic acid, induced differentiation of 32D IGF-IR/IRS-1 cells. We have also found that the expression of myeloperoxidase mRNA (a marker of differentiation, which sharply increases in 32D IGF-IR cells), does not increase in 32D IGF-IR/IRS-1 cells, suggesting that the expression of IRS-1 in 32D IGF-IR cells causes the extinction of the differentiation program initiated by the IGF-IR, while leaving intact its proliferation program.
dc.format.extent9 pages
dc.relation.ispartofFaculty/ Researcher Works
dc.relation.haspartJournal of Biological Chemistry, Vol. 275, No. 33
dc.rightsAttribution CC BY
dc.titleInsulin Receptor Substrate-1, p70S6K, and Cell Size in Transformation and Differentiation of Hemopoietic Cells
dc.type.genreJournal article
dc.ada.noteFor Americans with Disabilities Act (ADA) accommodation, including help with reading this content, please contact
dc.description.schoolcollegeTemple University. College of Science and Technology
dc.temple.creatorMorrione, Andrea

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