Interaction with newly synthesized and retained proteins in the endoplasmic reticulum suggests a chaperone function for human integral membrane protein IP90 (calnexin)

J Biol Chem. 1993 May 5;268(13):9585-92.

Abstract

A cDNA clone encoding the human endoplasmic reticulum (ER) resident protein IP90 was isolated and sequenced. It predicts a transmembrane protein with a large ER luminal region showing sequence similarity to calreticulin and a short cytoplasmic domain containing a COOH-terminal RKPRRE sequence that may be relevant to its retention in the ER. It is 95% homologous to the canine ER membrane phosphorprotein called pp90 or calnexin (Wada, I., Rindress, D., Cameron, P. H., Ou, W.-J., Doherty, J. J., II, Louvard, D., Bell, A. W., Dignard, D., Thomas, D. Y., and Bergeron, J. J. M. (1991) J. Biol. Chem. 266, 19599-19610). Previously, in lymphocytes, we have characterized IP90 as a protein associated with partially assembled multichain proteins including the T cell receptor, the membrane immunoglobulin, and the heavy chain of the major histocompatibility complex class I molecules (Hochstenbach, F., David, V., Watkins, S., and Brenner, M. B. (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 4734-4738). Here, we show that within a short metabolic labeling period, IP90 associates transiently with many different newly synthesized proteins. However, in a T cell line that cannot assemble a complete T cell receptor because it lacks the alpha subunit, the unassembled T cell receptor beta chains, which are retained in the ER, remain associated with IP90 throughout a prolonged chase time period. Together, these data offer further evidence suggesting that IP90 may act in assisting protein assembly and/or in the retention within the ER of unassembled protein subunits.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Calcium-Binding Proteins / genetics*
  • Calcium-Binding Proteins / metabolism*
  • Calnexin
  • Cell Line
  • Cloning, Molecular
  • Dogs
  • Endoplasmic Reticulum / metabolism*
  • Female
  • Gene Library
  • Heat-Shock Proteins / genetics
  • Heat-Shock Proteins / metabolism*
  • Histocompatibility Antigens Class I / genetics
  • Humans
  • Macromolecular Substances
  • Membrane Proteins / genetics*
  • Methionine / metabolism
  • Molecular Sequence Data
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism
  • Placenta / metabolism
  • Pregnancy
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, Antigen, B-Cell / genetics
  • Receptors, Antigen, T-Cell / genetics
  • Sequence Homology, Amino Acid
  • T-Lymphocytes / immunology
  • T-Lymphocytes / physiology
  • Transfection

Substances

  • Calcium-Binding Proteins
  • Heat-Shock Proteins
  • Histocompatibility Antigens Class I
  • Macromolecular Substances
  • Membrane Proteins
  • Phosphoproteins
  • RNA, Messenger
  • Receptors, Antigen, B-Cell
  • Receptors, Antigen, T-Cell
  • Calnexin
  • Methionine

Associated data

  • GENBANK/L10284