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A novel receptor function for the heat shock protein Grp78: silencing of Grp78 gene expression attenuates alpha2M*-induced signalling.

Publication ,  Journal Article
Misra, UK; Gonzalez-Gronow, M; Gawdi, G; Wang, F; Pizzo, SV
Published in: Cell Signal
August 2004

The activated proteinase inhibitor alpha2-macroglobulin (alpha2M*) binds to two receptors, the low density lipoprotein receptor-related protein (LRP-1) and the alpha2M* signalling receptor (alpha2MSR). Silencing LRP-1 gene expression in macrophages by RNA interference does not block alpha2M* activation of signalling cascades. We now demonstrate that transfection of macrophages with a double-stranded RNA homologous in sequence to the Grp78 gene markedly decreased induction of inositol 1,4,5-trisphosphate (IP3) and subsequent IP3-dependent elevation of [Ca2+]i induced by alpha2M*. Concomitantly, alpha2M*-induced increase in [3H]thymidine uptake was abolished in these transfected cells. Insulin treatment significantly upregulates alpha2MSR and it also caused a marked increase in Grp78 expression which could be blocked by RNA interference. alpha2M* treatment of cells activates the Ras- and PI 3-kinase-dependent signalling pathways. Suppressing Grp78 expression leads to the loss of these activation events in transfected macrophages. We thus conclude that Grp78 is the alpha2M* signalling receptor.

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Published In

Cell Signal

DOI

ISSN

0898-6568

Publication Date

August 2004

Volume

16

Issue

8

Start / End Page

929 / 938

Location

England

Related Subject Headings

  • alpha-Macroglobulins
  • Signal Transduction
  • RNA, Double-Stranded
  • RNA Interference
  • Phosphatidylinositol 3-Kinases
  • Molecular Chaperones
  • Mice
  • Macrophages, Peritoneal
  • Low Density Lipoprotein Receptor-Related Protein-1
  • Insulin
 

Citation

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Misra, U. K., Gonzalez-Gronow, M., Gawdi, G., Wang, F., & Pizzo, S. V. (2004). A novel receptor function for the heat shock protein Grp78: silencing of Grp78 gene expression attenuates alpha2M*-induced signalling. Cell Signal, 16(8), 929–938. https://doi.org/10.1016/j.cellsig.2004.01.003
Misra, Uma Kant, Mario Gonzalez-Gronow, Govind Gawdi, Fang Wang, and Salvatore Vincent Pizzo. “A novel receptor function for the heat shock protein Grp78: silencing of Grp78 gene expression attenuates alpha2M*-induced signalling.Cell Signal 16, no. 8 (August 2004): 929–38. https://doi.org/10.1016/j.cellsig.2004.01.003.
Misra UK, Gonzalez-Gronow M, Gawdi G, Wang F, Pizzo SV. A novel receptor function for the heat shock protein Grp78: silencing of Grp78 gene expression attenuates alpha2M*-induced signalling. Cell Signal. 2004 Aug;16(8):929–38.
Misra, Uma Kant, et al. “A novel receptor function for the heat shock protein Grp78: silencing of Grp78 gene expression attenuates alpha2M*-induced signalling.Cell Signal, vol. 16, no. 8, Aug. 2004, pp. 929–38. Pubmed, doi:10.1016/j.cellsig.2004.01.003.
Misra UK, Gonzalez-Gronow M, Gawdi G, Wang F, Pizzo SV. A novel receptor function for the heat shock protein Grp78: silencing of Grp78 gene expression attenuates alpha2M*-induced signalling. Cell Signal. 2004 Aug;16(8):929–938.
Journal cover image

Published In

Cell Signal

DOI

ISSN

0898-6568

Publication Date

August 2004

Volume

16

Issue

8

Start / End Page

929 / 938

Location

England

Related Subject Headings

  • alpha-Macroglobulins
  • Signal Transduction
  • RNA, Double-Stranded
  • RNA Interference
  • Phosphatidylinositol 3-Kinases
  • Molecular Chaperones
  • Mice
  • Macrophages, Peritoneal
  • Low Density Lipoprotein Receptor-Related Protein-1
  • Insulin