MUTAGENESIS OF PHE(381) AND PHE(382) IN THE EXTRACELLULAR DOMAIN OF THE INSULIN-RECEPTOR - EFFECTS ON RECEPTOR BIOSYNTHESIS, PROCESSING, AND LIGAND-DEPENDENT INTERNALIZATION

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 alpha-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(382)-Phe(382) sequence that causes a major defect in posttranslational processing of the receptor.