The mitogenic effects of the Bβ chain of fibrinogen are mediated through cell surface calreticulin

A. J. Gray, Woo Park Pyong Woo Park, T. J. Broekelmann, G. J. Laurent, J. T. Reeves, K. R. Stenmark, R. P. Mecham

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Abstract

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 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.

Original languageEnglish
Pages (from-to)26602-26606
Number of pages5
JournalJournal of Biological Chemistry
Volume270
Issue number44
DOIs
StatePublished - Jan 1 1995
Externally publishedYes

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