Functionally distinct insulin receptors generated by tissue-specific alternative splicing

Luitgard Mosthaf, Kathleen Grako, Thomas J. Dull, Lisa Coussens, Axel Ullrich, Donald A. McClain

Research output: Contribution to journalArticle

259 Citations (Scopus)

Abstract

Cloning of the insulin receptor cDNA has earlier revealed the existence of two alternative forms of the receptor differing by the presence or absence of 12 amino acids near the C-terminus of the receptor α-subunit. This insert has been shown by others to be encoded by a discrete exon, and alternative splicing of this exon leads to tissue-specific expression of two receptor isoforms. We have studied the functional significance of the receptor isoforms and have confirmed that they are generated by alternative splicing. When cDNAs encoding the two forms of the insulin receptors are expressed in Rat 1 cells, the receptor lacking the insert (HIR-A) has a significantly higher affinity for insulin than the receptor with the insert (HIR-B). This difference in affinity is maintained when insulin binding activity is assayed in solution using detergent solubilized, partially purified receptors. These data, combined with the tissue specificity of HIR-A and HIR-B expression, suggest that alternative splicing may result in the modulation of insulin metabolism or responsiveness by different tissues.

Original languageEnglish (US)
Pages (from-to)2409-2413
Number of pages5
JournalEMBO Journal
Volume9
Issue number8
StatePublished - 1990
Externally publishedYes

Fingerprint

Insulin Receptor
Alternative Splicing
Tissue
Exons
Protein Isoforms
Complementary DNA
Insulin
Organ Specificity
Cloning
Metabolism
Detergents
Rats
Organism Cloning
Modulation
Amino Acids

Keywords

  • Alternative splicing
  • Insulin binding
  • Insulin receptor

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

Mosthaf, L., Grako, K., Dull, T. J., Coussens, L., Ullrich, A., & McClain, D. A. (1990). Functionally distinct insulin receptors generated by tissue-specific alternative splicing. EMBO Journal, 9(8), 2409-2413.

Functionally distinct insulin receptors generated by tissue-specific alternative splicing. / Mosthaf, Luitgard; Grako, Kathleen; Dull, Thomas J.; Coussens, Lisa; Ullrich, Axel; McClain, Donald A.

In: EMBO Journal, Vol. 9, No. 8, 1990, p. 2409-2413.

Research output: Contribution to journalArticle

Mosthaf, L, Grako, K, Dull, TJ, Coussens, L, Ullrich, A & McClain, DA 1990, 'Functionally distinct insulin receptors generated by tissue-specific alternative splicing', EMBO Journal, vol. 9, no. 8, pp. 2409-2413.
Mosthaf L, Grako K, Dull TJ, Coussens L, Ullrich A, McClain DA. Functionally distinct insulin receptors generated by tissue-specific alternative splicing. EMBO Journal. 1990;9(8):2409-2413.
Mosthaf, Luitgard ; Grako, Kathleen ; Dull, Thomas J. ; Coussens, Lisa ; Ullrich, Axel ; McClain, Donald A. / Functionally distinct insulin receptors generated by tissue-specific alternative splicing. In: EMBO Journal. 1990 ; Vol. 9, No. 8. pp. 2409-2413.
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