Effect of pp120 on receptor-mediated insulin endocytosis is regulated by the juxtamembrane domain of the insulin receptor

Sonia M. Najjar, Curtis Choice, Payal Soni, Christina M. Whitman, Matthew N. Poy

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

pp120, a substrate of the insulin receptor tyrosine kinase, does not undergo ligand-stimulated phosphorylation by the insulin-like growth factor- 1 (IGF-1) receptor. However, replacement of the C-terminal domain of the IGF- 1 receptor β-subunit with the corresponding segment of the insulin receptor restored pp120 phosphorylation by the chimeric receptor. Since pp120 stimulates receptor-mediated insulin endocytosis when it is phosphorylated, we examined whether pp120 regulates IGF-1 receptor endocytosis in transfected NIH 3T3 cells. pp120 failed to alter IGF-1 receptor endocytosis via either wild-type or chimeric IGF-1 receptors. Thus, the effect of pp120 on hormone endocytosis is specific to insulin, and the C-terminal domain of the β- subunit of the insulin receptor does not regulate the effect of pp120 on insulin endocytosis. Mutation of Tyr960 in the juxtamembrane domain of the insulin receptor abolished the effect of pp120 to stimulate receptor endocytosis, without affecting pp120 phosphorylation by the insulin receptor. These findings suggest that pp120 interacts with two separate domains of the insulin receptor as follows: a C-terminal domain required for pp120 phosphorylation and a juxtamembrane domain required for internalization. We propose that the interaction of pp120 with the juxtamembrane domain is indirect and requires one or more substrates that bind to Tyr960 in the insulin receptor.

Original languageEnglish (US)
Pages (from-to)12923-12928
Number of pages6
JournalJournal of Biological Chemistry
Volume273
Issue number21
DOIs
StatePublished - May 22 1998
Externally publishedYes

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Insulin Receptor
Endocytosis
Phosphorylation
Somatomedin Receptors
Somatomedins
Insulin
IGF Type 1 Receptor
NIH 3T3 Cells
Substrates
Hormones
Ligands
Mutation

ASJC Scopus subject areas

  • Biochemistry

Cite this

Effect of pp120 on receptor-mediated insulin endocytosis is regulated by the juxtamembrane domain of the insulin receptor. / Najjar, Sonia M.; Choice, Curtis; Soni, Payal; Whitman, Christina M.; Poy, Matthew N.

In: Journal of Biological Chemistry, Vol. 273, No. 21, 22.05.1998, p. 12923-12928.

Research output: Contribution to journalArticle

Najjar, Sonia M. ; Choice, Curtis ; Soni, Payal ; Whitman, Christina M. ; Poy, Matthew N. / Effect of pp120 on receptor-mediated insulin endocytosis is regulated by the juxtamembrane domain of the insulin receptor. In: Journal of Biological Chemistry. 1998 ; Vol. 273, No. 21. pp. 12923-12928.
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