PubMed Journals: J Biol Chem

  Source:		PMID: 8027066

    		J Biol Chem. 1994 Jul 8;269(27):18062-71.
			The functions of the human insulin receptor
			are affected in different ways by mutation
			of each of the four N-glycosylation sites
			in the beta subunit.

			Leconte I(1), Carpentier JL, Clauser E.

			Author Information
			(1) INSERM U36, Chaire de Médecine Expérimentale,
			Collège de France, Paris.

			The functional role of the oligosaccharide
			chains linked to the insulin receptor (IR)
			beta subunit was investigated by site-directed
			mutagenesis of each of the 4 acceptor asparagines
			(N1 to N4 from the amino to the carboxyl
			terminus) and stable expression of the receptors
			in CHO cells. All mutant receptors are expressed
			normally at the cell surface, bind insulin
			with similar affinity, but have a beta subunit
			of smaller molecular mass, and a defect
			in ligand-induced internalization as compared
			to wild type receptor. In terms of receptor
			activation and signal transduction, the
			N1 and N2 mutants function normally, whereas
			the N4 mutant exhibits major alterations
			in in vitro tyrosine kinase activity and
			autophosphorylation and is unable to transduce
			the signal for either glycogen or DNA synthesis.
			By contrast, in vivo autophosphorylation
			and IRS-1 phosphorylation appear quantitatively
			normal, and only partial alterations of
			phosphatidylinositol 3-kinase and mitogen-activated
			protein kinase activation are observed.
			Mutation of the N3 site results in partial
			defect of IR activation. These data provide
			evidence for (i) glycosylation of each N-linked
			glycosylation site of the IR beta subunit,
			(ii) absence of correlation between internalization
			and transmembrane signaling, and (iii) a
			major role for oligosaccharide side chain(s)
			located close to the cell membrane in IR
			activation and transmembrane signaling.

			PMID: 8027066 [Indexed for MEDLINE]

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