MEGAKARYOCYTE AND HEPATOCYTE ORIGINS OF HUMAN-FIBRINOGEN BIOSYNTHESIS EXHIBIT HEPATOCYTE-SPECIFIC EXPRESSION OF GAMMA-CHAIN-VARIANT POLYPEPTIDES
- 1 August 1989
- journal article
- research article
- Vol. 74 (2) , 743-750
Abstract
The .gamma. chain of human fibrinogen is heterogeneous in length at the C-terminus due to differential RNA processing of the .gamma. chain-gene primary transcript. We have produced two specific monoclonal antibodies (MoAbs) against the .gamma.-chain epitopes generated by this alternative processing event: anti-.gamma.57.5408-416 (L2B), which reacts with .gamma.57.5 and .gamma.55 chains, and anti-.gamma.50397-411 (H9B7), which reacts preferentially with .gamma.50 chains. Using these MoAbs we have studied the expression of .gamma.-chain polypeptides by immunofluorescence microscopy in the tissues of fibrinogen biosynthesis and have determined that .gamma.57.5 polypeptide is expressed in hepatocytes but is absent or present in significantly reduced amounts in megakaryocytes. Therefore the .gamma.50 chain is found in plasma, platelet, and megakaryocyte fibrinogens, but the .gamma.57.5 chain is found only in plasma fibrinogen. The C-terminal amino acid sequence of .gamma.55 includes the L2B epitope 57.5408-416. Using MoAb L2B we have determined that .gamma.55, which is a post-translationally modified .gamma.57.5 chain, is found only in plasma fibrinogen and is absent or present in markedly reduced amounts in platelet or megakaryocyte fibrinogen. In addition, the conformation of the L2B epitope is preserved in .gamma.55, as determined by Western blot analysis. The hepatocyte-specific expression of the .gamma.57.5-chain polypeptide and the post-translational modification to .gamma.55 result in a compartmentalization of .gamma.-chain polypeptide expression. This is suggestive of different mechanisms regulating human fibrinogen .gamma.-chain gene expression in hepatocytes v megakaryocytes that may operate in a tissue-specific manner at the level of 3''RNA processing events.This publication has 26 references indexed in Scilit:
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