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

ABSTRACT: 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 CKII alpha 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 immunoprecipitated 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.

SUBMITTER: ole-MoiYoi OK

PROVIDER: S-EPMC413376 | biostudies-other | 1993 Apr

REPOSITORIES: biostudies-other

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

ole-MoiYoi O K OK Brown W C WC Iams K P KP Nayar A A Tsukamoto T T Macklin M D MD

The EMBO journal 19930401 4

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 t ...[more]

PMID: 8467809

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Project description:Recent technical advances have broadened our understanding of processes that govern mammalian cell migration in health and disease but many of the molecular and morphological alterations that precede and accompany movement of cells - in particular in three-dimensional (3D) environments - are still incompletely understood. In this manuscript, using high-resolution and time-lapse microscopy imaging approaches, we describe morphodynamic processes during rounded/amoeboid cell invasion and molecules associated with the cellular invasion structures. We used macrophages infected with the intracellular protozoan parasite Theileria annulata, which causes Tropical Theileriosis in susceptible ruminants such as domestic cattle. T. annulata transforms its host cell that, as a result, acquires many characteristics of human cancer cells including a markedly increased potential to migrate, disseminate and expand in the body of the host animal. Hence, virulence of the disease is associated with the capability of infected cells to disseminate inside the host. Using T. annulata-transformed macrophages as a model system, we described a novel mode of rounded/amoeboid macrophage migration. We show that filopodia-like membrane extensions at the leading edge lead the way and further evolve in blebbing membrane protrusions to promote progressive expansion of the matrix. Associated with focal invasion structures we detected ezrin, radixin, moesin-family proteins and their regulatory kinase MAP4K4. Furthermore, we linked Rho-kinase activity to contractile force generation, which is essential for infected cell motility. Thus, the motility mode of these parasite-transformed macrophages contrasts with those described so far in human macrophages such as the tunneling or mesenchymal modes, which require engulfment, compaction and ingestion of matrix or proteolytic matrix degradation, respectively. Together, our data reveal protrusion dynamics at the leading edge of invading cells in 3D at unprecedented temporal and spatial resolution and suggest a novel mode of rounded/amoeboid invasive cell motility that exploits actin-driven filopodia formation in combination with pressure-driven membrane blebs.

Project description:Theileria parva is a protozoan parasite that causes East Coast fever (ECF), an economically important disease of cattle in Africa. It is transmitted mainly by the tick Rhipicephalus appendiculatus. Research efforts to develop a subunit vaccine based on parasite neutralizing antibodies and cytotoxic T-lymphocytes have met with limited success. The molecular mechanisms underlying T. parva life cycle stages in the tick vector and bovine host are poorly understood, thus limiting progress toward an effective and efficient control of ECF. Transcriptomics has been used to identify candidate vaccine antigens or markers associated with virulence and disease pathology. Therefore, characterization of gene expression throughout the parasite's life cycle should shed light on host-pathogen interactions in ECF and identify genes underlying differences in parasite stages as well as potential, novel therapeutic targets. Recently, the first gene expression profiling of T. parva was conducted for the sporoblast, sporozoite, and schizont stages. The sporozoite is infective to cattle, whereas the schizont is the major pathogenic form of the parasite. The schizont can differentiate into piroplasm, which is infective to the tick vector. The present study was designed to extend the T. parva gene expression profiling to the piroplasm stage with reference to the schizont. Pairwise comparison revealed that 3,279 of a possible 4,084 protein coding genes were differentially expressed, with 1,623 (49%) genes upregulated and 1,656 (51%) downregulated in the piroplasm relative to the schizont. In addition, over 200 genes were stage-specific. In general, there were more molecular functions, biological processes, subcellular localizations, and pathways significantly enriched in the piroplasm than in the schizont. Using known antigens as benchmarks, we identified several new potential vaccine antigens, including TP04_0076 and TP04_0640, which were highly immunogenic in naturally T. parva-infected cattle. All the candidate vaccine antigens identified have yet to be investigated for their capacity to induce protective immune response against ECF.

Dataset Information

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

Publications

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

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