A novel threonine protein kinase regulates prohibitin 2 activity and T cell function

Abstract

Abstract Hispanic children have the highest rate of leukemia, which causes more deaths than any other cancer among children in the United States. Acute lymphoblastic leukemia (ALL) is the most common type of childhood cancer which is characterized by rapid uncontrolled accumulation of immature lymphocytes in the bone marrow and peripheral blood. Our studies have shown that the Prohibitin (Phb) family of proteins, Phb1 and Phb2, were upregulated during normal T-cell activation and likely function to maintain mitochondrial homeostasis and survival. In this work we hypothesized that a novel threonine protein kinase regulates prohibitin 2 (Phb2) activity and T-cell function. To determine the phosphorylation status of prohibitin proteins, phosphoamino acid analysis and mass spectrometry was performed followed by the generation of unique phospho-specific antibodies to characterize the putative regulatory pathways. A novel IL-2 inducible phospho-site in Phb2 was identified and characterized in T-cells. We propose that this novel threonine protein kinase participates in a previously unrecognized IL-2 signaling pathway that regulates T-cell activation and differentiation. The data also suggest that prohibitins are differentially expressed in lymphoid tumor cell lines and may serve as novel cancer biomarkers and possible molecular targets for therapeutic intervention in hematologic malignancies.