Differential regulation of insulin receptor substrate-1 degradation during mannitol and okadaic acid induced apoptosis in human neuroblastoma cells.
Cell Signal
; 17(6): 769-75, 2005 Jun.
Article
em En
| MEDLINE
| ID: mdl-15722201
ABSTRACT
Insulin receptor substrate (IRS) proteins are major docking molecules for the type I insulin like growth factor (IGF) receptor (IGF-IR) and mediate their effects on downstream signaling molecules. In this report, we investigated IRS-1 regulation during apoptosis in human neuroblastoma SH-EP cells. Treatment of SH-EP cells with mannitol or okadaic acid (OA) induces apoptosis with the typical characteristics of anoikis. Mannitol treatment results in IRS-1 degradation with concomitant appearance of smaller fragments, likely representing caspase cleavage products. In contrast OA-induced IRS-1 degradation is accompanied by a mobility shift in IRS-1, suggesting IRS-1 serine/threonine phosphorylation. Mannitol-induced, but not OA-induced, degradation is blocked by IGF-I. Pretreatment of the cells with caspase or proteasome inhibitors also partially blocks mannitol-induced IRS-1 degradation. These results suggest two independent pathways are involved in IRS-1 degradation; one pathway is dependent on caspase activation and is blocked by IGF-I, while a second pathway is caspase-independent and IGF-I-insensitive.
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Base de dados:
MEDLINE
Assunto principal:
Fosfoproteínas
/
Apoptose
/
Ácido Okadáico
/
Manitol
Limite:
Humans
Idioma:
En
Ano de publicação:
2005
Tipo de documento:
Article