The insulin receptor juxtamembrane region contains two independent tyrosine/β-turn internalization signals

J. M. Backer, S. E. Shoelson, M. A. Weiss, Xin Hua Qing Xin Hua, R. B. Cheatham, E. Haring, D. C. Cahill, M. F. White

Research output: Contribution to journalArticle

90 Scopus citations

Abstract

We have investigated the role of tyrosine residues in the insulin receptor juxtamembrane region (Tyr953 and Tyr960) during endocytosis. Analysis of the secondary structure of the juxtamembrane region by the Chou-Fasman algorithms predicts that both the sequences GPLY953 and NPEY960 form tyrosine-containing β-turns. Similarly, analysis of model peptides by 1-D and 2-D NMR show that these sequences form β-turns in solution, whereas replacement of the tyrosine residues with alanine destabilizes the β-turn. CHO cell lines were prepared expressing mutant receptors in which each tyrosine was mutated to phenylalanine of alanine, and an additional mutant contained alanine at both positions. These mutations had no effect on insulin binding or receptor autophosphorylation. Replacements with phenylalanine had no effect on the rate of [125I]insulin endocytosis, whereas single substitutions with alanine reduced [125I]insulin endocytosis by 40-50%. Replacement of both tyrosines with alanine reduced internalization by 70%. These data suggest that the insulin receptor contains two tyrosine/β-turns which contribute independently and additively to insulin-stimulated endocytosis.

Original languageEnglish (US)
Pages (from-to)831-838
Number of pages8
JournalJournal of Cell Biology
Volume118
Issue number4
DOIs
StatePublished - 1992

ASJC Scopus subject areas

  • Cell Biology

Fingerprint Dive into the research topics of 'The insulin receptor juxtamembrane region contains two independent tyrosine/β-turn internalization signals'. Together they form a unique fingerprint.

  • Cite this

    Backer, J. M., Shoelson, S. E., Weiss, M. A., Qing Xin Hua, X. H., Cheatham, R. B., Haring, E., Cahill, D. C., & White, M. F. (1992). The insulin receptor juxtamembrane region contains two independent tyrosine/β-turn internalization signals. Journal of Cell Biology, 118(4), 831-838. https://doi.org/10.1083/jcb.118.4.831