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Mutagenesis of Phe 381 and Phe 382 in the extracellular domain of the insulin receptor: effects on receptor biosynthesis, processing, and ligand‐dependent internalization
Author(s) -
Accili Domenico,
Mosthaf Luitgard,
Levy-Toledano Rachel,
Ullrich Axel,
Taylor Simeon I.
Publication year - 1994
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(94)80249-1
Subject(s) - insulin receptor , internalization , autophosphorylation , receptor , insulin receptor substrate , biochemistry , glucagon like peptide 1 receptor , mutant , 5 ht5a receptor , extracellular , biology , mutagenesis , mutation , insulin , chemistry , microbiology and biotechnology , agonist , endocrinology , insulin resistance , gene , protein kinase a , enzyme
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 Phe 382 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 Phe 381 and Phe 382 of the insulin receptor: Val for Phe 381 and Leu for Phe 382 . 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 Phe 382 is the only mutation of the Phe 381 ‐Phe 382 sequence that causes a major defect in posttranslational processing of the receptor.