The Pim family serine/threonine protein kinases were first identified in studies examining genes targeted for proviral insertion in murine leukemia virus-induced T lymphomas. Increased levels of Pim kinases predispose cells to lymphomagenesis and enhance the activity of mitogenic proteins such as p100, c-Myb, and Cdc25A. In addition, Pim kinases are also involved in modulation of synaptic strength in neurons and anti-apoptotic signaling in hematopoietic progenitor cells. Pim-3, a member of the proto-oncogene Pim family that expresses serine/threonine kinase activity, shares significant homology with Pim-1 serine/threonine protein kinases. Pim-3 may function as a mediator of synaptic plasticity in the brain and is presumably involved in the anti-apoptosis process and cell cycle progression as well as the proliferation of human hepatoma cell lines. The Pim-3 protein is widely expressed, however no expression is observed in the colon, thymus, or small intestine.
Function:
Proto-oncogene with serine/threonine kinase activity that can prevent apoptosis, promote cell survival and protein translation. May contribute to tumorigenesis through: the delivery of survival signaling through phosphorylation of BAD which induces release of the anti-apoptotic protein Bcl-X(L), the regulation of cell cycle progression, protein synthesis and by regulation of MYC transcriptional activity. Additionally to this role on tumorigenesis, can also negatively regulate insulin secretion by inhibiting the activation of MAPK1/3 (ERK1/2), through SOCS6. Involved also in the control of energy metabolism and regulation of AMPK activity in modulating MYC and PPARGC1A protein levels and cell growth.
Subunit:
Interacts with BAD. Interacts with PPP2CA; this interaction promotes dephosphorylation of PIM3, ubiquitination and proteasomal degradation. Interacts with SOCS6.
Subcellular Location:
Cytoplasm.
Tissue Specificity:
Detected in various tissues, including the heart, brain, lung, kidney, spleen, placenta, skeletal muscle, and peripheral blood leukocytes. Not found or barely expressed in the normal adult endoderm-derived organs such as colon, thymus, liver, or small intestine. However, expression is augmented in premalignant and malignant lesions of these organs.
Post-translational modifications:
Ubiquitinated, leading to proteasomal degradation.
Phosphorylated. Interaction with PPP2CA promotes dephosphorylation.
Similarity:
Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. PIM subfamily.
Contains 1 protein kinase domain.
SWISS:
Q86V86
Gene ID:
223775
Database links:
Entrez Gene: 415116 Human
Entrez Gene: 223775 Mouse
Omim: 610580 Human
SwissProt: Q86V86 Human
SwissProt: P58750 Mouse
Unigene: 530381 Human
Unigene: Hs.530381 Human
Unigene: 400129 Mouse
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