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| J. Biol. Chem. Nov (1995); 270(44):26602-6 | |
| The mitogenic effects of the B beta chain of fibrinogen are mediated through cell surface calreticulin. | |
| Gray AJ, Park PW, Broekelmann TJ, Laurent GJ, Reeves JT, Stenmark KR, Mecham RP | |
| University College London Medical School, Division of Cardiopulmonary Biochemistry, United Kingdom. | |
| 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 A alpha and B beta 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 beta chain. Receptor complexes were isolated from 125I-surface-labeled fibroblasts and purified on a fibrinogen B beta chain affinity column. Subsequent high performance liquid chromatography and SDS-polyacrylamide gel electrophoresis analysis indicated fibrinogen B beta 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 beta chain on human fibroblasts. The present study has shown that cell surface calreticulin binds to the B beta chain of fibrinogen mediating its mitogenic activity. | |
| [PUBMED: 7592883] |   |
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| BioGRID: A General Repository for Interaction Datasets. Chris Stark, Bobby-Joe Breitkreutz, Teresa Reguly, Lorrie Boucher, Ashton Breitkreutz, Mike Tyers. Nucleic Acids Res. Jan 1;34:D535-9. |