The Mitogenic Effects of the Bβ Chain of Fibrinogen Are Mediated through Cell Surface Calreticulin (*)

We have previously shown that soluble partially degraded fibrin(ogen) remains in solution after fibrin clot formation and is a potent fibroblast mitogen (Gray, A. J., Bishop, J. E., Reeves, J. T., Mecham, R. P., and Laurent, G. J.(1995) Am. J. Cell Mol. Biol. 12, 684-690). Mitogenic sites within the fibrin(ogen) molecule are located on the Aα and Bβ chains of the protein (Gray, A. J., Bishop, J. E., Reeves, J. T., and Laurent, G. J.(1993) J. Cell Sci. 104, 409-413). However, receptor pathways [Abstract] through which mitogenic effects are mediated are unknown. The present study sought to determine the nature of fibrin (ogen) receptors expressed on human fibroblasts which interact with the fibrinogen Bβ chain. Receptor complexes were isolated from 125I-surface-labeled fibroblasts and purified on a fibrinogen Bβ chain affinity column. Subsequent high performance liquid chromatography and SDS-polyacrylamide gel electrophoresis analysis indicated fibrinogen Bβ chain bound specifically to a 60-kDa surface protein. Sequence analysis of the amino terminus of this protein indicated 100% homology to human calreticulin. Immunoprecipitation experiments employing a polyclonal anti-calreticulin antibody provided further evidence that the 60-kDa protein isolated in this study was calreticulin. Further, polyclonal antibodies to human calreticulin significantly inhibited the mitogenic activity of fibrinogen Bβ chain on human fibroblasts. The present study has shown that cell surface calreticulin binds to the Bβ chain of fibrinogen mediating its mitogenic activity.

• Publication year

  1995

• Venue

  Journal of Biological Chemistry

• Publication date

  1995-11-03

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1074/jbc.270.44.26602PMID 7592883
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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