Evidence for the induction of casein kinase II in bovine lymphocytes transformed by the intracellular protozoan parasite Theileria parva

Theileria parva is an obligate, intracellular, parasitic protozoan that causes East Coast fever, an acute leukemia-like disease of cattle. T.parva and the related parasite, Theileria annulata, are unique among protozoa in that their intralymphocytic stages induce transformation of bovid lymphocytes. Comparison of in vitro protein kinase activities between uninfected IL-2-dependent T lymphoblasts and T.parva-infected lymphocytes revealed a 4.7- to 12-fold increase in total phosphorylation and the induction of a group of Theileria infection-specific phosphoproteins. The enzyme that phosphorylates these substrates is a serine/threonine kinase with substrate and effector specificities of casein kinase (CK) II. Northern blot analyses revealed a 3.9-to 6.0-fold increase in CKIIα mRNA in the infected cells relative to the controls. Furthermore, a marked increase of CKII antigen was observed on Western blots of materials prepared from the infected cell lines. The antibovine CKII antibody used in these studies immuno-precipitated a protein kinase that phosphorylated casein in a reaction that was inhibited by low (nM) quantities of heparin. Our data show marked increases of bovine CKII at the transcriptional, translational and functional levels in T.parva-infected lymphocytes, relative to quiescent cells or IL-2-dependent parental lymphoblasts. Bovine CKII thus appears to be constitutively activated in these cells and we propose that this kinase may be an important element in the signal-transducing pathways activated by Theileria in bovid lymphocytes and perhaps in some leukemic cells.