The tyrosine residue at 1250 of the insulin-like growth factor I receptor is required for ligand-mediated internalization.
The twin tyrosine residues at 1250 and 1251 of the insulin-like growth factor I receptor (IGF-IR) are missing in the corresponding homologous region of the insulin receptor. In this unique region, the tyrosine at 1251 (Y1251) is essential for both transforming and antiapoptotic activities of the IGF-IR, while Y1250 is dispensable for either of these functions. We show here that a receptor with a mutation at Y1250, but not at Y1251, has lost the ability for ligand-mediated internalization when the mutant receptors are overexpressed in R- cells, derived from a mouse embryo with a targeted disruption of the IGF-IR gene. These results provide evidence that each twin tyrosine at Y1250 and Y1251 of the IGF-IR separately exerts different roles in biologically important signal transductions.
Miura
M
M
Department of Dental Radiology and Radiation Research, Faculty of Dentistry, Tokyo Medical and Dental University, Japan. masa.drad@dent.tmd.ac.jp
Baserga
R
R
D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D008024:Ligands; D051379:Mice; D016297:Mutagenesis, Site-Directed; D017526:Receptor, IGF Type 1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011972:Receptor, Insulin / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship; D014443:Tyrosine / Q000737:chemistry / Q000378:metabolism*
D008024:Ligands; D014443:Tyrosine; D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin