Caveolin-1 Interacts with the Insulin Receptor and Can Differentially Modulate Insulin Signaling in Transfected Cos-7 Cells and Rat Adipose Cells
| Autor: | Michael J. Quon, Yunhua Li, Li-Na Cong, Fredrik H. Nystrom, Hui Chen |
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| Rok vydání: | 1999 |
| Předmět: |
Male
medicine.medical_specialty Monosaccharide Transport Proteins medicine.medical_treatment Caveolin 1 Gene Expression Muscle Proteins Adipose tissue Transfection Caveolins Endocrinology Insulin receptor substrate Internal medicine Adipocytes medicine Animals Insulin Phosphorylation Molecular Biology Immunosorbent Techniques Glucose Transporter Type 4 biology Autophosphorylation Membrane Proteins General Medicine Receptor Insulin Recombinant Proteins Rats Cell biology Insulin receptor COS Cells Mutagenesis Site-Directed cardiovascular system biology.protein Signal transduction GLUT4 Signal Transduction |
| Zdroj: | Molecular Endocrinology. 13:2013-2024 |
| ISSN: | 1944-9917 0888-8809 |
| Popis: | Caveolae may function as microdomains for signaling that help to determine specific biological actions mediated by the insulin receptor (IR). Caveolin-1, a major component of caveolae, contains a scaffolding domain (SD) that binds to a caveolin-1 binding motif in the kinase domain of the IR in vitro. To investigate the potential role of caveolin-1 in insulin signaling we overexpressed wild-type (Cav-WT) or mutant (Cav-Mut; F92A/V94A in SD) caveolin-1 in either Cos-7 cells cotransfected with IR or rat adipose cells (low and high levels of endogenous caveolin-1, respectively). Cav-WT coimmunoprecipitated with the IR to a much greater extent than Cav-Mut, suggesting that the SD is important for interactions between caveolin-1 and the IR in intact cells. We also constructed several IR mutants with a disrupted caveolin-1 binding motif and found that these mutants were poorly expressed and did not undergo autophosphorylation. Interestingly, overexpression of Cav-WT in Cos-7 cells significantly enhanced insulin-stimulated phosphorylation of Elk-1 (a mitogen-activated protein kinase-dependent pathway) while overexpression of Cav-Mut was without effect. In contrast, in adipose cells, overexpression of either Cav-WT or Cav-Mut did not affect insulin-stimulated phosphorylation of a cotransfected ERK2 (but did significantly inhibit basal phosphorylation of ERK2). Furthermore, we also observed a small inhibition of insulin-stimulated translocation of GLUT4 when either Cav-WT or Cav-Mut was overexpressed in adipose cells. Thus, interaction of caveolin-1 with IRs may differentially modulate insulin signaling to enhance insulin action in Cos-7 cells but inhibit insulin’s effects in adipose cells. |
| Databáze: | OpenAIRE |
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