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 A and B 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 B chain. Receptor complexes were isolated from I-surface-labeled fibroblasts and purified on a fibrinogen B chain affinity column. Subsequent high performance liquid chromatography and SDS-polyacrylamide gel electrophoresis analysis indicated fibrinogen B 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 B chain on human fibroblasts. The present study has shown that cell surface calreticulin binds to the B chain of fibrinogen mediating its mitogenic activity.

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