serine/threonine protein kinase pim-2; Pim-2h (PIM2)
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Function
- proto-oncoprotein with serine/threonine kinase activity
- role in cell survival & cell proliferation
- exerts its oncogenic activity through
- regulation of MYC transcriptional activity
- regulation of cell cycle progression
- regulation of cap-dependent protein translation
- survival signaling by phosphorylation of a pro-apoptotic protein, BAD
- phosphorylation of MYC leads to an increase of MYC protein stability & thus an increase transcriptional activity
- stabilization of MYC by PIM2 might partly explain synergism between these 2 oncoprotein in tumorigenesis
- regulates cap-dependent protein translation (mTORC1-independent) in parallel to the PI3K-Akt pathway
- mediates survival signaling through phosphorylation of BAD, which induces release of the anti-apoptotic protein BCL2L1
- promotes cell survival in response proliferative signals via positive regulation of the I-kappa-B kinase/NF-kappa-B cascade
- requires phosphorylation of MAP3K8/COT
- isoform 1 is less active
- promotes growth factor-independent proliferation by phosphorylation of cell cycle factors such as CDKN1A & CDKN1B
- role in positive regulation of chondrocyte survival & autophagy in the epiphyseal growth plate
- autophosphorylated (putative)
- interacts with MYC (putative)
Structure
- belongs to the protein kinase superfamily, CAMK Ser/Thr protein kinase family, PIM subfamily
- contains 1 protein kinase domain
Expression
- highly expressed in hematopoietic tissues, in leukemic & lymphoma cell lines, testis, small intestine, colon & colorectal adenocarcinoma cells
- weakly expressed in normal liver, but highly expressed in hepatocellular carcinoma tissues
- down-regulated in response to enterovirus 71 (EV71) infection