Effect of cDNA copy number on secretion rate of activated protein C

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Abstract
The secretion rate of activated protein C (APC) by BHK cells was increased 35‐fold by increasing the cDNA copy number per cell from 50 to 240. In this range, the relation between APC secretion and cDNA copy number was not linear and the rate of APC secretion per cDNA copy increased sevenfold. This apparent cooperative effect of multiple cDNA copies could be related to their integration in tandem. For cDNA copy numbers higher than 240, the APC secreation rate per cDNA and per cell decreased dramatically. The γ‐carboxylation of glutamic acid residues, a posttranslational modification required for APC biological activity, was also investigated. The proportion of APC that was fully γ‐carboxylated decreased as the secretion rate of APC increased. © 1995 John Wiley & Sons, Inc.