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The presence of malfolded proteins in the endoplasmic reticulum signals the induction of glucose-regulated proteins

Nature volume 332, pages 462–464 (1988)Cite this article

Abstract

Two glucose-regulated proteins, GRP78 and GRP94, are major constituents of the endoplasmic reticulum (ER) of mammalian cells. These proteins are synthesized constitutively in detectable amounts under normal growth conditions; they can also be induced under a variety of conditions of stress including glucose starvation and treatment with drugs that inhibit cellular glycosylation, with calcium ionophores or with amino-acid analogues1,2. Unlike the closely-related heat shock protein (HSP) family2–4, the GRPs are not induced significantly by high temperature. Recently, GRP78 has been identified as the immunoglobulin heavy chain binding protein (BiP) (ref. 5 and Y.K. et al., in preparation) which binds transiently to a variety of nascent, wild-type secretory and trans-membrane proteins and permanently to malfolded proteins that accumulate within the ER6–8. We have tested the hypothesis that the presence of malfolded proteins may be the primary signal for induction of GRPs by expressing wild-type and mutant forms of influenza virus haemagglutinin (HA) in simian cells. Only malfolded HAs, whose transport from the ER is blocked, induced the synthesis of GRPs 78 and 94. Additional evidence is presented that malfoldingper se, rather than abnormal glycosylation1, is the proximal inducer of this family of stress proteins.

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Authors and Affiliations

  1. Department of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, Texas, 75235, USA

    Yasunori Kozutsumi, Mark Segal, Karl Normington, Mary-Jane Gething & Joe Sambrook

  2. Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, Texas, 75235, USA

    Yasunori Kozutsumi & Mary-Jane Gething

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  1. Yasunori Kozutsumi
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Kozutsumi, Y., Segal, M., Normington, K. et al. The presence of malfolded proteins in the endoplasmic reticulum signals the induction of glucose-regulated proteins. Nature 332, 462–464 (1988). https://doi.org/10.1038/332462a0

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