title: The role of E3 ubiquitin ligase Cbl proteins in interleukin-2-induced Jurkat T-cell activation.
abstract: Interleukin- (IL-) 2 is the major growth factor for T-cell activation and proliferation. IL-2 has multiple functions in the regulation of immunological processes. Although most studies focus on T-cell immunomodulation, T-cell activation by IL-2 is the foundation of priming the feedback loop. Here, we investigated the effect of MAPK/ERK and PI3K/Akt signaling pathways on IL-2-induced cell activation and the regulatory mechanisms of upstream ubiquitin ligase Cbl-b and c-Cbl. Morphological analysis of Jurkat T cells was performed by cytospin preparations with Wright-Giemsa stain. CD25 expression on Jurkat T cells was determined by flow cytometry. Changes in cell activation proteins such as p-ERK, ERK, p-Akt, Akt, and ubiquitin ligase Casitas B-cell Lymphoma (Cbl) proteins were analyzed by western blot. Following IL-2-induced activation of Jurkat T cells, p-ERK expression was upregulated, while there was no change in p-Akt, ERK, or Akt expression. Thus, the MAPK/ERK signaling pathway, but not PI3K/Akt, was involved in IL-2-induced T-cell activation. Either using PD98059 (a specific inhibitor for p-ERK) or depletion of ERK with small interfering RNA (siRNA) reduced the expression of CD25. This study also showed that ubiquitin ligase proteins Cbl-b and c-Cbl might be involved in IL-2-induced Jurkat T-cell activation by negatively regulating the MAPK/ERK signaling pathway.
authors.affiliation: Department of Medical Oncology, The First Hospital of China Medical University, Shenyang 110001, China.
authors.forename: Ming-Fang
authors.initials: MF
authors.lastname: Zhao
authors.forename: Xiu-Juan
authors.initials: XJ
authors.lastname: Qu
authors.forename: Jing-Lei
authors.initials: JL
authors.lastname: Qu
authors.forename: You-Hong
authors.initials: YH
authors.lastname: Jiang
authors.forename: Ye
authors.initials: Y
authors.lastname: Zhang
authors.forename: Ke-Zuo
authors.initials: KZ
authors.lastname: Hou
authors.forename: Hao
authors.initials: H
authors.lastname: Deng
authors.forename: Yun-Peng
authors.initials: YP
authors.lastname: Liu
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D006801:Humans; D007376:Interleukin-2 / Q000276:immunology* / Q000378:metabolism; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D020935:MAP Kinase Signaling System; D051058:Oncogene Protein v-akt / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D050721:Proto-Oncogene Proteins c-cbl / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation
chemical_list: D007376:Interleukin-2; D050721:Proto-Oncogene Proteins c-cbl; D019869:Phosphatidylinositol 3-Kinases; D051058:Oncogene Protein v-akt