The A isoform of the insulin receptor (IR) is frequently overexpressed in cancer cells and is activated by IGF-II as well as by insulin, whereas the B isoform is predominant in differentiated tissues and responds poorly to IGF-II. The IR substrate-1 (IRS-1), a docking protein for the IR, is known to send a mitogenic signal and to be a powerful inhibitor of cell differentiation. We have investigated the biological effects of the two IR isoforms in parental 32D hemopoietic cells, which do not express IRS-1, and in 32D-derived cells in which IRS-1 is ectopically expressed. The effects of the two isoforms on cell survival, differentiation markers and nuclear translocation of IRS-1 were compared. The results confirm that the A isoform responds to IGF-II and preferentially sends mitogenic, antiapoptotic signals, whereas the B form, poorly responsive to IGF-II, tends to send differentiation signals.

Signaling Differences from the A and B isoforms of the Insulin Receptor (IR) in 32D Cells in the Presence or Absence of IR Substrate-1

SCIACCA, LAURA;A. BELFIORE;
2003-01-01

Abstract

The A isoform of the insulin receptor (IR) is frequently overexpressed in cancer cells and is activated by IGF-II as well as by insulin, whereas the B isoform is predominant in differentiated tissues and responds poorly to IGF-II. The IR substrate-1 (IRS-1), a docking protein for the IR, is known to send a mitogenic signal and to be a powerful inhibitor of cell differentiation. We have investigated the biological effects of the two IR isoforms in parental 32D hemopoietic cells, which do not express IRS-1, and in 32D-derived cells in which IRS-1 is ectopically expressed. The effects of the two isoforms on cell survival, differentiation markers and nuclear translocation of IRS-1 were compared. The results confirm that the A isoform responds to IGF-II and preferentially sends mitogenic, antiapoptotic signals, whereas the B form, poorly responsive to IGF-II, tends to send differentiation signals.
2003
insulin receptor, insulin receptor isoforms, isoform A
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11769/4797
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