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Titolo:
The role of the insulin receptor substrate-1 in the differentiation of rathippocampal neuronal cells
Autore:
Morrione, A; Navarro, M; Romano, G; Dews, M; Reiss, K; Valentinis, B; Belletti, B; Baserga, R;
Indirizzi:
Thomas Jefferson Univ, Kimmel Canc Ctr, Philadelphia, PA 19107 USA Thomas Jefferson Univ Philadelphia PA USA 19107 hiladelphia, PA 19107 USA
Titolo Testata:
ONCOGENE
fascicolo: 35, volume: 20, anno: 2001,
pagine: 4842 - 4852
SICI:
0950-9232(20010809)20:35<4842:TROTIR>2.0.ZU;2-1
Fonte:
ISI
Lingua:
ENG
Soggetto:
GROWTH-FACTOR-I; ACTIVATED PROTEIN-KINASE; PHOSPHOTYROSINE-DEPENDENT INTERACTION; RIBOSOMAL S6 KINASE; PHOSPHATIDYLINOSITOL 3-KINASE; HEMATOPOIETIC-CELLS; SIGNALING PATHWAYS; INSULIN-LIKE-GROWTH-FACTOR-1 RECEPTOR; TYROSINE PHOSPHORYLATION; PLECKSTRIN HOMOLOGY;
Keywords:
IGF-IR, insulin-like growth factor-1 receptor; IGF-I, insulin-like growth factor-I; IGF-II, insulin-like growth factor-II; IRS-1, insulin receptor substrate-1; PI3K, phosphatidylinositol-3 kinase;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
63
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:
A. Morrione et al., "The role of the insulin receptor substrate-1 in the differentiation of rathippocampal neuronal cells", ONCOGENE, 20(35), 2001, pp. 4842-4852

Abstract

H19-7/IGF-IR cells are rat hippocampal cells expressing a human IGF-I receptor, which differentiate to a neuronal phenotype when stimulated by IGF-I at 39 degreesC. H19-7/IGF-IR cells have low levels of expression of insulinreceptor substrate-1 (IRS-1), a major substrate of the IGF-IR. IGF-I induces serine-phosphorylation and down-regulation of the endogenous IRS-1 upon differentiation of H19-7/IGF-IR cells. The profound influence of IRS-1 on differentiation of H19-7/IGF-IR cells was confirmed by transfecting these cells with a plasmid expressing mouse IRS-1. Over-expression of wild type IRS-1 in H19-7/IGF-IR cells abolishes IGF-I-induced differentiation at 39 degrees C. A mutant of IRS-1 lacking the PTB domain loses the ability to inhibit the differentiation program. H19-7/IGF-IR/IRS-1 cells at 39 degrees C show a stronger and prolonged activation of Akt, when compared to H19-7/IGF-IRcells. The role of Akt in the inhibition of the differentiation program was confirmed by using the inhibitor of Class I PI3 kinases LY29400, which restores IGF-I-induced differentiation of H19-7/IGF-IR/IRS-1 cells. H19-7/IGF-IR/IRS-1 cells show a strong reduction in MAP kinases signaling, which is related to the superactivation of Akt. This was confirmed by expressing in H19-7/IGF-IR cells a constitutively active Akt, which inhibited MAP kinasesactivation in these cells. These experiments confirm the importance of MAPK in the mechanism of IGF-I-mediated differentiation of H19-7/IGF-IR cells.

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Documento generato il 25/11/20 alle ore 19:02:38