Interaction of factor XII and high molecular weight kininogen with cytokeratin 1 and gC1qR of vascular endothelial cells and with aggregated Abeta protein of Alzheimer's disease.

摘要

High molecular weight kininogen (HK) attaches to endothelial cells at separate sites on the heavy and light chains by a process which requires 15-50 microM zinc. Previously identified binding proteins include gClqR, cytokeratin 1, and the urokinase plasminogen activator receptor (U-par), however, their relative contribution to binding are not yet clarified. We have purified the binding proteins by affinity chromatography, in the presence of zinc ion, and identified cytokeratin 1 and gC1qR by amino acid sequencing of an internal peptide and by immunoblot as heavy chain and light chain binding proteins, respectively. Antibody to cytokeratin 1 inhibited HK binding to endothelial cells by 30%, antibody to gClqR inhibited HK binding to endothelial cells by 72%, and a mixture of both inhibited binding by 86%. The binding and activation of the proteins of the kinin-forming cascade along the cell surface is zinc-dependent. Similarly, proteins of the plasma kinin-forming cascade can be activated by binding to aggregated A(beta) protein of Alzheimer's disease. Activation of the cascade using purified proteins or upon addition of Abeta to plasma requires aggregation of A(beta) and the reactions are zinc-dependent. In plasma, HK is cleaved and bradykinin is liberated. The data demonstrate that aggregated A(beta) can bind and activate proenzymes of the plasma kinin-forming cascade to release bradykinin and these reactions are dependent on zinc ion.