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Insulin modulates PC-1 processing and recruitment in cultured human cells
C Menzaghi1, R Di Paola, G Baj
1Laboratory of Immunogenetics, Department of Genetics, Biology and Biochemistry, University of Torino Medical School, Italy. endocrinologia@operapadrepio.it
American Journal of Physiology. Endocrinology and Metabolism
|November 21, 2002
Summary
Insulin promotes plasma cell glycoprotein (PC-1) processing and membrane arrival, which then hinders insulin receptor signaling. This bidirectional interaction may explain how hormones self-desensitize.
Area of Science:
- Cell biology
- Molecular endocrinology
- Signal transduction
Background:
- Insulin signaling is crucial for glucose homeostasis.
- Plasma cell glycoprotein (PC-1) is implicated in various cellular processes.
- The interplay between insulin and PC-1 is not fully understood.
Purpose of the Study:
- To investigate how insulin signaling affects PC-1.
- To determine PC-1's role in insulin receptor signaling.
Main Methods:
- Human cultured cell lines were used.
- Insulin treatment was applied.
- Inhibitors of phosphatidylinositol 3-kinase (wortmannin) and S6 kinase (rapamycin) were utilized.
- Intracellular trafficking was manipulated (monensin).
- Western blotting and endoglycosidase H sensitivity assays were performed.
Main Results:
- Insulin significantly increased PC-1 plasma membrane expression.
- This increase was dependent on phosphatidylinositol 3-kinase, S6 kinase, and intracellular trafficking.
- Insulin induced a novel 146-kDa PC-1-related band sensitive to endoglycosidase H.
- PC-1 gene expression remained unchanged.
- Inhibition of PC-1 translocation enhanced insulin receptor autophosphorylation.
Conclusions:
- Insulin stimulates PC-1 posttranslational modification and plasma membrane translocation.
- Translocated PC-1 impairs insulin receptor signaling.
- A bidirectional cross-talk exists between insulin and PC-1, potentially contributing to insulin self-desensitization.