The role of receptor kinase activity and the NPEY960 motif in insulin-accelerated receptor-mediated insulin internalization

Journal of Receptor and Signal Transduction Research
R M SmithL Jarett

Abstract

This study used biochemical and quantitative ultrastructural approaches to examine the roles that insulin receptor beta subunit kinase activity, the NPEY motif in the juxtamembrane region, and tyrosine phosphorylation within that domain plays in insulin-accelerated receptor-mediated insulin internalization in CHO cells. Internalization of insulin in cells that expressed kinase-deficient receptors (CHOA1018) or receptors lacking the NPEY Ala954-Asp965 domain (CHO delta 960) was reduced by 80% compared to cells expressing wild-type human insulin receptors (CHOHIRc). Ultrastructural analysis revealed that the decreased internalization in CHOA1018 cells was due to the reduced ability of the kinase deficient receptor to migrate from the microvilli of cultured cells and aggregate on the cell surface. Deletion of the NPEY motif in the juxtamembrane region of the beta subunit severely reduced receptor migration, interfered with the normal aggregation of receptors on the cell surface, and virtually eliminated accumulation of the occupied receptors in the coated invaginations. Replacement of Tyr960 in the NPEY domain/with phenylalanine (CHOF960) had no significant effect on insulin internalization, receptor mobility, aggregation or accum...Continue Reading

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