Mutagenesis of Phe381 and Phe382 in the extracellular domain of the insulin receptor: effects on receptor biosynthesis, processing, and ligand‐dependent internalization

FEBS Letters

Levy-Toledano, Rachel²  Accili, Domenico²  Taylor, Simeon I.²  Ullrich, Axel¹  Mosthaf, Luitgard¹ 

[1] Department of Molecular Biology, Max-Planck-Institut für Biochemie, W-8033 Martinsried bei München, Germany;Diabetes Branch, National Institute of Diabetes and Digestive and Kidney Disease, National Institutes of Health, Bethesda, MD 20892, USA

关键词: Insulin receptor;    Mutagenesis;    Intracellular transport;    Genetic disease;    Insulin resistance;   

DOI  :  10.1016/0014-5793(94)80249-1

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Mutations of the extracellular domain of the insulin receptor impair processing and transport of receptors to the plasma membrane. We have previously reported that a mutation substituting Val for Phe³⁸² in the α-subunit of the insulin receptor impairs intracellular processing and insulin-induced autophosphorylation of the mutant receptor. In this investigation, we have generated two independent mutations of amino acids Phe³⁸¹ and Phe³⁸² of the insulin receptor: Val for Phe³⁸¹ and Leu for Phe³⁸². These substitutions cause a slight impairment of intracellular processing and transport of the mutant receptors. Furthermore, insulin-dependent internalization of the mutant receptors is unaffected by these mutations. Thus, of the three substitutions studied to date, Val for Phe³⁸² is the only mutation of the Phe³⁸¹-Phe³⁸² sequence that causes a major defect in posttranslational processing of the receptor.

【 授权许可】

Unknown