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.
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.
Dipartimento di Medicina Interna e Medicina Specialistica, University of Catania, Ospedale Garibaldi, 95123 Catania, Italy.
Laura
L
Sciacca
Marco
M
Prisco
An
A
Wu
Antonino
A
Belfiore
Riccardo
R
Vigneri
Renato
R
Baserga
D000209:Acute-Phase Proteins / Q000235:genetics; D000818:Animals; D015703:Antigens, CD; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival; D004268:DNA-Binding Proteins / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D051797:Inhibitor of Differentiation Protein 2; D055504:Insulin Receptor Substrate Proteins; D007377:Interleukin-3 / Q000494:pharmacology; D007536:Isomerism; D000071068:Lipocalin-2; D054834:Lipocalins; D051379:Mice; D015513:Oncogene Proteins / Q000235:genetics; D009195:Peroxidase / Q000235:genetics; D010750:Phosphoproteins / Q000378:metabolism* / Q000494:pharmacology; D011518:Proto-Oncogene Proteins; D011972:Receptor, Insulin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics
D000209:Acute-Phase Proteins; D015703:Antigens, CD; D004268:DNA-Binding Proteins; C497452:Idb2 protein, mouse; D051797:Inhibitor of Differentiation Protein 2; D055504:Insulin Receptor Substrate Proteins; D007377:Interleukin-3; C526295:Irs1 protein, mouse; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D015513:Oncogene Proteins; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C071332:Lcn2 protein, mouse; D009195:Peroxidase; C435941:INSR protein, human; D011972:Receptor, Insulin