Isoform-specific insulin receptor signaling involves different plasma membrane domains

Sabine Uhles, Tilo Moede, Barbara Leibiger, Per Olof Berggren, Ingo B. Leibiger

Research output: Contribution to journalArticlepeer-review

72 Scopus citations

Abstract

In pancreatic β-cells, insulin selectively up-regulates the transcription of its own gene and that of the glucokinase gene by signaling through the two isoforms of the insulin receptor, i.e., A-type (Ex11-) and B-type (Ex11+), using different signaling pathways. However, the molecular mechanism(s) that allows the discrete activation of signaling cascades via the two receptor isoforms remains unclear. Here we show that activation of the insulin promoter via A-type and of the glucokinase promoter via B-type insulin receptor is not dependent on receptor isoform-specific differences in internalization but on the different localization of the receptor types in the plasma membrane. Our data demonstrate that localization and function of the two receptor types depend on the 12-amino acid string encoded by exon 11, which acts as a sorting signal rather than as a physical spacer. Moreover, our data suggest that selective activation of the insulin and glucokinase promoters occurs by signaling from noncaveolae lipid rafts that are differently sensitive toward cholesterol depletion.

Original languageEnglish (US)
Pages (from-to)1327-1337
Number of pages11
JournalJournal of Cell Biology
Volume163
Issue number6
DOIs
StatePublished - Dec 22 2003

Keywords

  • Fluorescent protein
  • Glucokinase
  • Insulin
  • Lipid rafts
  • Signal transduction

ASJC Scopus subject areas

  • Cell Biology

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