Post-Translational Modification by Covalent Phosphorylation of Human Apolipoprotein B-100

Abstract

Within human plasma, apolipoprotein B exists as two antigenically-related isoproteins, designated apoB- 100 (Mr 512,000) and apoB-48 (Mr 250,000). The major apoB secreted in vitro by normal human hepatocytes and Hep G-2 cells is apoB-100 (Edge, et al., 1985). The peripheral metabolism of VLDL and apoB in part determine the level of circulating LDL (Dolphin, 1985). The LDL, possesing apoB-100 as the principal apolipoprotein constituent, are the major cholesterol transporting lipoproteins in human plasma. Since both LDLcholesterol (Grundy, 1986) and apoB-100 (Brunzell et al., 1984) levels are directly and positively correlated with premature coronary artery heart disease, an understanding of the control of hepatic apoB-100 synthesis and secretion is important. The human apolipoproteins have been demonstrated to undergo several co-translational and post-translational modifications including proteolytic cleavage (Gordon et al., 1983; Stoffel et al., 1983; Zannis et al, 1983; Bojanovski et al., 1984), glycosylation (Swaminathan and Aladjem, 1976; Lee and Breckenridge, 1967; Brewer et al., 1974; Zannis and Breslow, 1981), covalent phospholyration (Beg et al., 1989; Davis et al., 1984; Sparks et al., 1988 and Jackson et al., 1990), fatty acid acylation (Hoeg et al., 1986 and Hoeg et al., 1988) and deamidation (Ghisseli et al., 1985). These structural alterations may have important physiologic as well as pathologic roles.