Selective gene activation by spatial segregation of insulin receptor B signaling

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

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

Insulin exerts pleiotropic effects at the cellular level. Signaling via the two isoforms of the insulin receptor (IR) may explain the activation of different signaling cascades, while it remains to be explored how selectivity is achieved when utilizing the same IR isoform. We now demonstrate that insulin-stimulated transcription of c-fos and glucokinase genes is activated simultaneously in the insulin-producing β-cell via IR-B localized in different cellular compartments. Insulin activates the glucokinase gene from plasma membrane-standing IR-B, while c-fos gene activation is dependent on clathrin-mediated IR-B-endocytosis and signaling from early endosomes. Moreover, glucokinase gene up-regulation requires the integrity of the juxtamembrane IR-B NPEY-motif and signaling via PI3K-C2α-like/PDK1/PKB, while c-fos gene activation requires the intact C-terminal YTHM-motif and signaling via PI3K Ia/Shc/MEK1/ERK. By using IR-B as an example it is thus possible to demonstrate how spatial segregation allows simultaneous and selective signaling via the same receptor isoform in the same cell.

Original languageEnglish (US)
Pages (from-to)1609-1621
Number of pages13
JournalFASEB Journal
Volume21
Issue number7
DOIs
StatePublished - May 1 2007

Keywords

  • c-fos gene
  • Endosomes
  • Gene expression regulation
  • Glucokinase gene
  • Insulin signaling
  • Life cell imaging
  • Pancreatic beta cell

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

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  • Cite this

    Uhles, S., Moede, T., Leibiger, B., Berggren, P. O., & Leibiger, I. B. (2007). Selective gene activation by spatial segregation of insulin receptor B signaling. FASEB Journal, 21(7), 1609-1621. https://doi.org/10.1096/fj.06-7589com