Intracellular association of a mutant insulin-like growth factor receptor with endogenous receptors.
The type 1 insulin-like growth factor receptor (IGF-IR) is emerging as a powerful survival factor against a variety of apoptotic agents in many cell types. A mutant IGF-IR designated 486/STOP is known to induce apoptosis and inhibit the growth of human tumor cells in mice. We have investigated the mechanism of action of 486/STOP. To study it, we have developed a new retroviral vector in which we have combined a self-inactivating 5'-long terminal repeat with an inducible heat-shock promoter (heat shock protein 70) from Drosophila. Using this technique, we find that the polypeptide encoded by 486/STOP is partially retained within the cell and partially secreted. However, the secreted polypeptide is subsequently taken up by the cells. In both cases, a specific intracellular interaction of 486/STOP with the endogenous IGF-IRs can be demonstrated by coimmunoprecipitation.
Reiss
K
K
Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Tu
X
X
Romano
G
G
Peruzzi
F
F
Wang
J Y
JY
Baserga
R
R
D000362:Agar / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects / Q000235:genetics; D002460:Cell Line; D017077:Culture Media, Conditioned / Q000737:chemistry; D015870:Gene Expression; D005838:Genotype; D018613:Microscopy, Confocal; D009154:Mutation; D010957:Plasmids / Q000235:genetics; D011485:Protein Binding; D017526:Receptor, IGF Type 1 / Q000235:genetics* / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism
D017077:Culture Media, Conditioned; D011993:Recombinant Fusion Proteins; D000362:Agar; D017526:Receptor, IGF Type 1