A SERINE-KINASE-CONTAINING PROTEIN COMPLEX INTERACTS WITH THE TERMINAL PROTEIN DOMAIN OF POLYMERASE OF HEPATITIS-B VIRUS

Polymerase of human hepatitis B virus is required for viral replicatio n and pregenomic RNA encapsidation. Using recombinant GST fusion prote ins, we show that the terminal protein domain of polymerase can intera ct specifically with a protein complex containing kinase activity and a tightly associated 35-kD protein (p35). This kinase is termed termin al-protein-associated kinase (TPAK). The phosphoamino acid analysis of phosphorylated p35 demonstrates that TPAK is a serine kinase. Analysi s of deletion mutants shows that amino acids 1-95 of the terminal prot ein domain are required for the interaction with TPAK/p35 and phosphor ylation of p35. TPAK/p35 are found predominantly in the cytoplasm. Fur thermore, TPAK can be inhibited by heparin and manganese ions, but is resistant to spermidine, DRB, H89 or H7. These results indicate that T PAK is not protein kinase A or protein kinase C.