Insulin inhibition of protein degradation in cells expressing wild-type and mutant insulin receptors

Frederick G Hamel, J. Fawcett, C. I. Andersen, P. Berhanu, Robert G Bennett, W. C. Duckworth

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

The mechanism by which insulin decreases protein degradation is unknown. We examined insulin binding and degradation (125I-A14]insulin) and protein degradation (3H-leucine labeling) in Chinese hamster ovary (CHO) cells transfected with wild-type (WI) and mutant human insulin receptors. The ΔExon-16 mutant is missing the juxtamembrane domain that mediates endocytosis. The Δ343 mutant receptor lacks the tyrosine kinase structural domain but retains the juxtamembrane internalization domain. The mutant ΔNPEY lacks the single NPEY sequence located 16 residues after the end of the transmembrane domain. Null transfected cells (NEO) not expressing human receptors were studied as controls. The WT and ΔNPEY cells equivalently internalized and degraded insulin; Δ343 cells internalized and degraded insulin, but at a reduced rate; ΔExon-16 cells internalized and degraded significantly less insulin than the other mutants; NEO cells showed essentially no internalization and degradation. In contrast, all cell types showed the same efficacy at inhibition of protein degradation, albeit at different potencies. These results suggest insulin actions are mediated by multiple and redundant effector systems, but that receptor tyrosine kinase activity is not required for inhibition of protein degradation.

Original languageEnglish (US)
Pages (from-to)1088-1094
Number of pages7
JournalJournal of Endocrinological Investigation
Volume26
Issue number11
DOIs
StatePublished - Nov 2003

Fingerprint

Insulin Receptor
Proteolysis
Insulin
Receptor Protein-Tyrosine Kinases
Exons
Null Lymphocytes
Endocytosis
Cricetulus
Leucine
Ovary

Keywords

  • Chinese hamster ovary cells
  • Insulin degrading enzyme
  • Insulin receptor
  • Proteasome
  • Protein degradation
  • Tyrosine kinase

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

Insulin inhibition of protein degradation in cells expressing wild-type and mutant insulin receptors. / Hamel, Frederick G; Fawcett, J.; Andersen, C. I.; Berhanu, P.; Bennett, Robert G; Duckworth, W. C.

In: Journal of Endocrinological Investigation, Vol. 26, No. 11, 11.2003, p. 1088-1094.

Research output: Contribution to journalArticle

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