Phosphorylation of the hepatitis B virus core protein by glyceraldehyde-3-phosphate dehydrogenase protein kinase activity.
In order to characterize the hepatitis B virus (HBV) hepatocellular receptor, several proteins have previously been identified in HepG2 hepatoma cells and in primary cultured normal human hepatocytes (PCHs) that reacted with an anti-idiotypic antibody against a preS1(21-47)-specific MAb (F35.25). Here, we report the identification of one of these preS1-binding proteins, a 35 kDa protein (preS1-BP35), as glyceraldehyde-3-phosphate dehydrogenase (GAPD). GAPD is well-known as a key enzyme involved in glycolysis and gluconeogenesis. Nevertheless, GAPD has also been shown to have many other functions such as protein kinase activity (GAPD-PK). HBV core particles derived from infected hepatocytes possess an associated kinase activity that phosphorylates HBcAg, and the nucleocapsid may acquire sequential functions through selective phosphorylation. Therefore, we have investigated the potential role of GAPD-PK in HBV replication. In this study, we found that the endogenous PK associated with human liver-derived HBV core particles (hL-HBcAg) and GAPD-PK were sensitive to the same types of inhibitors. Interestingly, capsid protein phosphorylation decreased in a concentration-dependent manner (at concentrations of 5-30 mM) in the presence of specific inhibitors for GAPD-PK (NADH and GAP). Furthermore, we demonstrated in vitro that GAPD-PK could phosphorylate the major core protein P22 in hL-HBcAg particles. The data suggest that GAPD is an additional cellular kinase which might interfere in the life-cycle of HBV.
INSERM Unité 131, Clamart, France.
J C
JC
Duclos-Vallée
F
F
Capel
H
H
Mabit
M A
MA
Petit
D000595:Amino Acid Sequence; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000737:chemistry / Q000378:metabolism*; D006512:Hepatitis B Core Antigens / Q000378:metabolism*; D006514:Hepatitis B Surface Antigens / Q000378:metabolism; D006515:Hepatitis B virus / Q000378:metabolism*; D019694:Hepatitis B, Chronic / Q000821:virology*; D006801:Humans; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011498:Protein Precursors / Q000378:metabolism; D014407:Tumor Cells, Cultured
D006512:Hepatitis B Core Antigens; D006514:Hepatitis B Surface Antigens; D011498:Protein Precursors; C050806:presurface protein 1, hepatitis B surface antigen; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases