EFFECT OF CDNA COPY NUMBER ON SECRETION RATE OF ACTIVATED PROTEIN-C

The secretion rate of activated protein C (APC) by BHK cells was incre ased 35-fold by increasing the cDNA copy number per cell from 50 to 24 0. In this range, the relation between APC secretion and cDNA copy num ber was not linear and the rate of APC secretion per cDNA copy increas ed sevenfold. This apparent cooperative effect of multiple cDNA copies could be related to their integration in tandem. For cDNA copy number s higher than 240, the APC secretion rate per cDNA and per cell decrea sed dramatically. The gamma-carboxylation of glutamic acid residues, a posttranslational modification required for APC biological activity, was also investigated. The proportion of APC that was fully gamma-carb oxylated decreased as the secretion rate of APC increased. (C) 1995 Jo hn Wiley and Sons, Inc.