BIOSYNTHESIS OF PLASMA FACTOR-XIII - EVIDENCE FOR TRANSCRIPTION AND TRANSLATION IN HEPATOMA-CELLS

Factor XIIIa belongs to a family of ubiquitous transglutaminases, whic h catalyze formation of covalent bonds between the epsilon-amino group of specific lysines and the gamma-carboxyl group of glutamines. Facto r XIII is synthesized as a zymogen and after activation, it participat es in both the coagulation and fibrinolytic mechanisms. Most transglut aminases are intracellular, but factor XIII is both intracellular and extracellular. The biosynthesis of extracellular (plasma) factor XIII, with the structure of a noncovalent heterotetramer, A(2)B(2), is comp lex. Here, evidence is presented from PCR analysis and Northern blotti ng that mRNAs for both A and B subunits are present in the liver. The distribution of mRNA, specific for factor XII subunits, in various hum an tissues was also analyzed. Among the tissues examined, the only sig nal for B subunit was found in the liver. For subunit A, the signal wa s observed in placenta, liver, kidney, lung, skeletal muscle and heart with varying intensities; in brain or pancreas there was no signal. W ith an immunoperoxidase method, factor XIII A subunit was identified i n the PLC/PRF/5 cell line. By ELISA and reverse immunoblotting, with a ntibodies specific for the A-B complex, it was also shown that these c ells produce and secrete factor XIII. From all of these results, we co nclude that the liver is a source of plasma factor XIII, and that the complex A(2)B(2) is secreted from these cells.