Pim-1 is a proto-oncogene which encodes for the serine/threonine kinase of the same name. The pim-1 oncogene was first described in relation to murine T-cell lymphomas, as it was the locus most frequently activated by the Moloney murine leukemia virus. Subsequently, the oncogene has been implicated in multiple human cancers, including prostate cancer, acute myeloid leukemia and other hematopoietic malignancies. Primarily expressed in spleen, thymus, bone marrow, prostate, oral epithelial, hippocampus and fetal liver cells, Pim-1 has also been found to be highly expressed in cell cultures isolated from human tumors. Pim-1 is mainly involved in cell cycle progression, apoptosis and transcriptional activation, as well as more general signal transduction pathways.
Pim-1 is primarily involved in cytokine signaling, and has been implicated in many signal transduction pathways. Because Pim-1 translation is initiated by STAT3 and STAT5, its production is regulated by the cytokines that regulate the STAT pathway, or STAT factors. These include interleukins (IL-2, IL-3,IL-5, IL-6, IL-7, IL12, IL-15), prolactin, TNFα, EGF and IFNγ, among others. Interestingly, Pim-1 itself can bind to negative regulators of the JAK/STAT pathway, resulting in a negative feedback loop.
Pim1 phosphorylates a number of signal transduction proteins like the transcription factor cMyb, the suppressor of cytokine signaling SOCS, pro-apoptotic protein Bad, phosphatase cdc25, HSP90, the kinase c-TAK as well as proteins necessary for mitosis and thereby modulates signal transduction pathways involved in the regulation of cell cycle, apoptosis, differentiation and proliferation. Comparison of phosphorylation sites showed that the Pim recognition sequences need to contain basic residues at positions -3 and -5. Combinatorial peptide library methods showed also a strong preference for histidine at position -2, proline at -1 as well as glycine at position +1.
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