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Titolo:
Insulin receptor substrate-1, p70(S6K), and cell size in transformation and differentiation of hemopoietic cells
Autore:
Valentinis, B; Navarro, M; Zanocco-Marani, T; Edmonds, P; McCormick, J; Morrione, A; Sacchi, A; Romano, G; Reiss, K; Baserga, R;
Indirizzi:
Thomas Jefferson Univ, Kimmel Canc Ctr, Philadelphia, PA 19107 USA Thomas Jefferson Univ Philadelphia PA USA 19107 hiladelphia, PA 19107 USA Thomas Jefferson Univ, Dept Pathol, Philadelphia, PA 19107 USA Thomas Jefferson Univ Philadelphia PA USA 19107 hiladelphia, PA 19107 USA Inst Regina Elena, Ctr Ric Sperimentale, Lab Oncogenesi Mol, I-00158 Rome,Italy Inst Regina Elena Rome Italy I-00158 Oncogenesi Mol, I-00158 Rome,Italy
Titolo Testata:
JOURNAL OF BIOLOGICAL CHEMISTRY
fascicolo: 33, volume: 275, anno: 2000,
pagine: 25451 - 25459
SICI:
0021-9258(20000818)275:33<25451:IRSPAC>2.0.ZU;2-0
Fonte:
ISI
Lingua:
ENG
Soggetto:
GROWTH-FACTOR-I; P70 S6 KINASE; MULTIPLE SIGNALING PATHWAYS; HEMATOPOIETIC-CELLS; PHOSPHATIDYLINOSITOL 3-KINASE; INSULIN-LIKE-GROWTH-FACTOR-1 RECEPTOR; PHOSPHORYLATION SITES; OKADAIC ACID; APOPTOSIS; ACTIVATION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
57
Recensione:
Indirizzi per estratti:
Indirizzo: Baserga, R Thomas Jefferson Univ, Kimmel Canc Ctr, 233 S 10th St,624 BLSB,Philadelphia, PA 19107 USA Thomas Jefferson Univ 233 S 10th St,624 BLSB Philadelphia PA USA 19107
Citazione:
B. Valentinis et al., "Insulin receptor substrate-1, p70(S6K), and cell size in transformation and differentiation of hemopoietic cells", J BIOL CHEM, 275(33), 2000, pp. 25451-25459

Abstract

After 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 land 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 p70(S6K), which is activated by the IRS-l pathway. We find that the ectopic expression of IRS-1 and the inhibition of differentiation correlated with a sustained activation of p70(S6K), and an increase in cell size. Phosphorylation in 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 p70(S6K) in the alternative between transformation or differentiation of 32D IGF-IR cells was confirmed by findings that inhibition of p70(S6K) activation or IRS-1signaling, by rapamycin or okadaic acid, induced differentiation of 32D IGF-IR/IRS-1 cells. We have also found that the expression of myeloperoxidasemRNA (a marker of differentiation, which sharply increases in 32D IGF-IR cells), does not increase in 32D IGF-IRI/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.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 30/11/20 alle ore 15:42:51