Back to Search
Start Over
Expression and function of insulin/insulin-like growth factor I hybrid receptors during differentiation of 3T3-L1 preadipocytes
- Source :
- The Biochemical journal. 333
- Publication Year :
- 1998
-
Abstract
- During the assembly of cell surface receptors, insulin proreceptors are sometimes joined to insulin-like growth factor (IGF) receptor precursors to form covalently linked hybrid receptors. To address the biological consequences of hybrid receptor formation, we studied 3T3-L1 cells known to undergo a 50–70-fold increase in insulin binding while maintaining nearly constant levels of IGF-I binding during differentiation from preadipocytes into adipocytes. The presence of insulin/IGF receptor hybrids in 3T3-L1 adipocytes was demonstrated by the immunoprecipitation of phosphorylated receptors and a novel enzyme-linked immunoassay. Hybrid receptor levels were very low in the early stages of differentiation and increased rapidly between days 4 and 6, reaching a level about 100-fold higher in the mature adipocyte. Coincident with the hybrid assembly, the formation of archetypal (α2,β2) IGF receptors decreased. In fully differentiated adipocytes, virtually all of the IGF receptors were in hybrid form. Stimulation by IGF-I of receptors isolated from mature adipocytes caused autophosphorylation of IGF receptor β subunits in hybrid complexes, whereas autophosphorylated IGF holoreceptors were not demonstrable. Insulin and IGF-I were equipotent in stimulating glucose uptake in the differentiated adipocytes, leading to the conclusion that hybrid insulin/IGF receptors can transduce a transmembrane signal when activated by IGF-I. We conclude that hybrid formation constitutes a novel post-translational mechanism whereby increased synthesis of insulin receptors limits the cell surface expression of the homologous IGF receptor. Furthermore, biological actions in 3T3-L1 adipocytes, previously attributed to archetypal IGF receptors, are in fact mediated through hybrid receptors.
- Subjects :
- medicine.medical_specialty
medicine.medical_treatment
Cellular differentiation
Biochemistry
Receptor, IGF Type 1
Insulin-like growth factor
Mice
Cell surface receptor
Internal medicine
medicine
Adipocytes
Animals
Insulin
Insulin-Like Growth Factor I
Phosphorylation
Receptor
Molecular Biology
Hexoses
biology
Growth factor
Autophosphorylation
Cell Differentiation
Cell Biology
3T3 Cells
Precipitin Tests
Receptor, Insulin
Stimulation, Chemical
Insulin receptor
Endocrinology
biology.protein
Research Article
Subjects
Details
- ISSN :
- 02646021
- Volume :
- 333
- Database :
- OpenAIRE
- Journal :
- The Biochemical journal
- Accession number :
- edsair.doi.dedup.....f802d67e07423fb4cc9fa27b2ea79e89