IGF-I receptor signalling in transformation and differentiation.
The type 1 insulin-like growth factor receptor (IGF-IR) sends several signals, some of which are contradictory. When the concentrations of insulin receptor substrate 1 (IRS-1), a major substrate of the IGF-IR, are high, the signal is mitogenic, anti-apoptotic, and can even cause malignant transformation. However, in the absence of IRS-1, the IGF-IR sends a differentiation signal, which leads to granulocytic differentiation in haemopoietic cells. The mitogenic signal of the IGF-IR/IRS-1 combination depends largely, but not exclusively, on the activation of the phosphatidylinositol-3 kinase (PI3K).
Valentinis
B
B
Kimmel Cancer Center, Thomas Jefferson University, 233 S. 10th Street, 624 BLSB, Philadelphia, PA 19107, USA.
Baserga
R
R
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D015415:Biomarkers / Q000032:analysis; D002454:Cell Differentiation / Q000502:physiology*; D002471:Cell Transformation, Neoplastic; D015536:Down-Regulation / Q000502:physiology; D006801:Humans; D051379:Mice; D009195:Peroxidase / Q000032:analysis; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D017526:Receptor, IGF Type 1 / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
D015415:Biomarkers; D009195:Peroxidase; D019869:Phosphatidylinositol 3-Kinases; D017526:Receptor, IGF Type 1