Skip to main content

The role of Grp 78 in alpha 2-macroglobulin-induced signal transduction. Evidence from RNA interference that the low density lipoprotein receptor-related protein is associated with, but not necessary for, GRP 78-mediated signal transduction.

Publication ,  Journal Article
Misra, UK; Gonzalez-Gronow, M; Gawdi, G; Hart, JP; Johnson, CE; Pizzo, SV
Published in: J Biol Chem
November 1, 2002

The low density lipoprotein receptor-related protein (LRP) is a scavenger receptor that binds to many proteins, some of which trigger signal transduction. Receptor-recognized forms of alpha(2)-Macroglobulin (alpha(2)M*) bind to LRP, but the pattern of signal transduction differs significantly from that observed with other LRP ligands. For example, neither Ni(2+) nor the receptor-associated protein, which blocks binding of all known ligands to LRP, block alpha(2)M*-induced signal transduction. In the current study, we employed alpha(2)-macroglobulin (alpha(2)M)-agarose column chromatography to purify cell surface membrane binding proteins from 1-LN human prostate cancer cells and murine macrophages. The predominant binding protein purified from 1-LN prostate cancer cells was Grp 78 with small amounts of LRP, a fact that is consistent with our previous observations that there is little LRP present on the surface of these cells. The ratio of LRP:Grp 78 is much higher in macrophages. Flow cytometry was employed to demonstrate the presence of Grp 78 on the cell surface of 1-LN cells. Purified Grp 78 binds to alpha(2)M* with high affinity (K(d) approximately 150 pm). A monoclonal antibody directed against Grp 78 both abolished alpha(2)M*-induced signal transduction and co-precipitated LRP. Ligand blotting with alpha(2)M* showed binding to both Grp 78 and LRP heavy chains in these preparations. Use of RNA interference to silence LRP expression had no effect on alpha(2)M*-mediated signaling. We conclude that Grp 78 is essential for alpha(2)M*-induced signal transduction and that a "co-receptor" relationship exists with LRP like that seen with several other ligands and receptors such as the uPA/uPAR (urinary type plasminogen activator or urokinase/uPA receptor) system.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

November 1, 2002

Volume

277

Issue

44

Start / End Page

42082 / 42087

Location

United States

Related Subject Headings

  • alpha-Macroglobulins
  • Tumor Cells, Cultured
  • Signal Transduction
  • RNA Interference
  • Molecular Chaperones
  • Mice
  • Male
  • Low Density Lipoprotein Receptor-Related Protein-1
  • Humans
  • Heat-Shock Proteins
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Misra, U. K., Gonzalez-Gronow, M., Gawdi, G., Hart, J. P., Johnson, C. E., & Pizzo, S. V. (2002). The role of Grp 78 in alpha 2-macroglobulin-induced signal transduction. Evidence from RNA interference that the low density lipoprotein receptor-related protein is associated with, but not necessary for, GRP 78-mediated signal transduction. J Biol Chem, 277(44), 42082–42087. https://doi.org/10.1074/jbc.M206174200
Misra, Uma K., Mario Gonzalez-Gronow, Govind Gawdi, Justin P. Hart, Carrie E. Johnson, and Salvatore V. Pizzo. “The role of Grp 78 in alpha 2-macroglobulin-induced signal transduction. Evidence from RNA interference that the low density lipoprotein receptor-related protein is associated with, but not necessary for, GRP 78-mediated signal transduction.J Biol Chem 277, no. 44 (November 1, 2002): 42082–87. https://doi.org/10.1074/jbc.M206174200.

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

November 1, 2002

Volume

277

Issue

44

Start / End Page

42082 / 42087

Location

United States

Related Subject Headings

  • alpha-Macroglobulins
  • Tumor Cells, Cultured
  • Signal Transduction
  • RNA Interference
  • Molecular Chaperones
  • Mice
  • Male
  • Low Density Lipoprotein Receptor-Related Protein-1
  • Humans
  • Heat-Shock Proteins