TI  - The mitogenic effects of the  <prot>B beta chain of fibrinogen</prot>  are mediated
      through cell surface  <prot>calreticulin</prot> .
PG  - 26602-6
AB  - 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  <prot>fibrinogen B beta chain</prot> . Receptor
      complexes were isolated from 125I-surface-labeled fibroblasts and purified
      on a <prot>fibrinogen B beta chain</prot> affinity column. Subsequent high performance
      liquid chromatography and SDS-polyacrylamide gel electrophoresis analysis
      indicated <prot>fibrinogen B beta chain</prot> bound specifically to a 60-kDa surface
      protein. Sequence analysis of the amino terminus of this protein indicated
      100% homology to human <prot>calreticulin</prot>. Immunoprecipitation experiments
      employing a polyclonal anti-<prot>calreticulin</prot> antibody provided further
      evidence that the 60-kDa protein isolated in this study was <prot>calreticulin</prot>.
      Further, polyclonal antibodies to human  <prot>calreticulin</prot>  significantly
      inhibited the mitogenic activity of  <prot>fibrinogen B beta chain</prot>  on human
      fibroblasts. The present study has shown that cell surface  <prot>calreticulin</prot> 
      binds to the  <prot>B beta chain of fibrinogen</prot>  mediating its mitogenic activity.
AD  - University College London Medical School, Division of Cardiopulmonary
