Affinage

PIM2

Serine/threonine-protein kinase pim-2 · UniProt Q9P1W9

Length
311 aa
Mass
34.2 kDa
Annotated
2026-06-10
100 papers in source corpus 44 papers cited in narrative 44 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PIM2 is a constitutively active, cytoplasmic serine/threonine kinase that integrates cytokine and stress signaling into a coordinated pro-survival, pro-proliferative, and metabolic program, with broad oncogenic consequences (PMID:12869584, PMID:7781606). Its central survival output is phosphorylation and inactivation of the pro-apoptotic BH3 protein BAD (Ser112) together with rapamycin-resistant phosphorylation of the translational repressor 4E-BP1, sustaining cell survival, cell size, and mitochondrial potential independently of PI3K/Akt/TOR (PMID:12869584, PMID:12954615). PIM2 reinforces apoptotic resistance through additional substrates—phosphorylating Bim (Ser65) to drive its proteasomal degradation (PMID:27770661) and stabilizing p21 via Thr145 phosphorylation (PMID:20307683)—and it couples survival to mTORC1 activation by directly phosphorylating TSC2 (Ser1798) to relieve its suppression of mTOR-C1 (PMID:23818547). A second major axis is glycolytic (Warburg) reprogramming: PIM2 binds and phosphorylates hexokinase-2 (Thr473), PKM2 (Thr454), and inhibits AMPKα1 (Thr467), and phosphorylates PFKFB3 (Ser478) and PFKFB4 (Thr140) to stabilize them through the ubiquitin-proteasome pathway, collectively enhancing aerobic glycolysis and tumor growth (PMID:29985480, PMID:24142698, PMID:31358902, PMID:33931981, PMID:36109523). PIM2 also activates NF-κB signaling by phosphorylating and activating Cot, which augments IκB kinase activity, an event required for PIM2-mediated survival and oncogenesis (PMID:15548703). Beyond canonical kinase activity, PIM2 functions kinase-independently—degrading tristetraprolin to de-repress proliferation (PMID:29570932) and acting as a transcriptional co-factor for HIF-1α (PMID:24505470)—and it has context-specific immunoregulatory roles, phosphorylating Foxp3 to weaken Treg suppression (PMID:25987564) and negatively regulating alloreactive T cell responses (PMID:29781812). PIM2 itself is regulated transcriptionally downstream of JAK/STAT5 and STAT3/STAT4, p53, HIF-1α, and CHES1/FOXN3, and post-translationally by ubiquitin-independent degradation by the 20S proteasome (PMID:26500282, PMID:24403608, PMID:24505470, PMID:30096294, PMID:31068472).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1995 High

    Established PIM2 as a distinct kinase functionally redundant with PIM1, placing it within the same oncogenic pathway and explaining why it can substitute for PIM1 loss.

    Evidence PCR-based gene identification and proviral complementation tagging in Eµ-myc/Pim-1−/− mice

    PMID:7781606

    Open questions at the time
    • Did not define direct substrates
    • Mechanism of constitutive activity not addressed
  2. 2003 High

    Defined PIM2's core survival mechanism: direct phosphorylation of BAD (Ser112) and rapamycin-resistant 4E-BP1 phosphorylation, establishing a PI3K/Akt/TOR-independent survival pathway.

    Evidence Constitutive expression in hematopoietic/FDCP1 cells, in vitro kinase assay, growth-factor withdrawal survival assays

    PMID:12869584 PMID:12954615

    Open questions at the time
    • Mechanism by which 4E-BP1 phosphorylation is maintained not resolved
    • Relative contribution of three isoforms to physiological survival unclear
  3. 2004 High

    Showed PIM2-driven survival and oncogenesis require NF-κB, placing PIM2 upstream of the Cot/IKK/NF-κB axis.

    Evidence Reporter assays, Co-IP, NF-κB blockade, primary cell rescue, in vivo lymphoma model

    PMID:15548703

    Open questions at the time
    • Direct phosphorylation site on Cot not mapped
    • Whether NF-κB activation is universal across PIM2 contexts unknown
  4. 2009 High

    Provided structural basis for PIM2 inhibition, revealing ATP-pocket differences from PIM1 exploitable for isoform-selective inhibitors.

    Evidence X-ray crystallography of PIM2 with an organoruthenium inhibitor

    PMID:19841674

    Open questions at the time
    • No substrate-bound structure
    • Basis of constitutive activity not structurally explained
  5. 2013 High

    Connected PIM2 to mTORC1 and Warburg metabolism via direct phosphorylation of TSC2 (Ser1798) and PKM2 (Thr454), extending its function beyond survival into proliferation and glycolysis.

    Evidence In vitro kinase assays, knockdown/inhibitor, phospho-defective mutants, glycolysis assays in MM and other cells

    PMID:23818547 PMID:24142698

    Open questions at the time
    • Crosstalk between TSC2/mTORC1 and direct 4E-BP1 phosphorylation not disentangled
    • In vivo metabolic consequences only partially characterized
  6. 2015 High

    Defined PIM2's post-translational regulation and immunoregulatory role: ubiquitin-independent 20S proteasomal degradation, STAT5-controlled mRNA, and Foxp3 phosphorylation weakening Treg suppression.

    Evidence In vitro 20S degradation reconstitution, fractionation, STAT5 inhibition; in vitro Foxp3 kinase assay with Treg knockout and colitis model

    PMID:25987564 PMID:26500282

    Open questions at the time
    • Degron motif targeting PIM2 to 20S proteasome not defined
    • Foxp3 phosphosites and their individual contributions incompletely mapped
  7. 2018 High

    Revealed a kinase-independent mode of action—PIM2 degrades tristetraprolin to de-repress proliferation—and a metabolic axis stabilizing HK2 via chaperone-mediated autophagy.

    Evidence Co-IP, kinase-dead mutants, proteasome/CMA assays, in vitro kinase assay (HK2 Thr473), xenografts

    PMID:29570932 PMID:29985480

    Open questions at the time
    • How a kinase mediates substrate degradation without phosphorylation is mechanistically unresolved
    • Determinants choosing kinase-dependent vs -independent outputs unknown
  8. 2019 High

    Extended the glycolytic and immune-evasion network: PIM2 inhibits AMPKα1 (Thr467), and stabilizes HSF1 (Thr120) to drive PD-L1 expression.

    Evidence In vitro kinase assays with site mutants, ChIP, KO mouse and xenograft models

    PMID:31358902 PMID:31409638

    Open questions at the time
    • Integration of multiple metabolic substrates into a single flux model lacking
    • PD-L1 immune-evasion consequence not tested in immunocompetent tumor settings here
  9. 2020 Medium

    Linked PIM2 to NF-κB stabilization and innate immunity: phosphorylation of FBP1 (Ser144) stabilizing p65/PD-L1, and direct binding to NLRP3 promoting inflammasome activation.

    Evidence In vitro kinase/ubiquitination assays, Co-IP, PIM2 KO mice, ARDS model

    PMID:32754266 PMID:33333710

    Open questions at the time
    • Whether NLRP3 is a direct phosphorylation substrate not established
    • RIPK2 phosphorylation (idx 35) inferred without in vitro kinase assay
  10. 2021 High

    Consolidated PIM2 as a master glycolytic regulator stabilizing PFKFB3 (Ser478) and PFKFB4 (Thr140) via the ubiquitin-proteasome pathway across cancer and endometriosis.

    Evidence Mass spectrometry, in vitro kinase assays with site mutants, ubiquitination assays, xenograft/in vivo models

    PMID:33931981 PMID:36109523

    Open questions at the time
    • Common mechanism by which phosphorylation blocks ubiquitination across these substrates not unified
    • Tissue specificity of substrate selection unclear
  11. 2024 High

    Identified a PIM2-USP27X-MYC axis in which PIM2 phosphorylation of USP27X stabilizes MYC to boost HK2-driven glycolysis, integrating deubiquitination control into PIM2's metabolic program.

    Evidence Co-IP, in vitro kinase assay, deubiquitylation assay, MYC stability and glycolysis assays, PIM2 KO mice

    PMID:38969771

    Open questions at the time
    • USP27X phosphosite not specified in the finding
    • Relationship to direct HK2 phosphorylation pathway not reconciled

Open questions

Synthesis pass · forward-looking unresolved questions
  • How PIM2's many parallel substrate axes (survival, mTORC1, glycolysis, NF-κB, immune regulation) are prioritized in a given cell type, and what governs its kinase-dependent versus kinase-independent and co-factor functions, remains unresolved.
  • No unified model of substrate selection across tissues
  • Determinants of kinase-independent vs catalytic activity undefined
  • Structural basis of constitutive activity and isoform-specific functions incompletely understood

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 13 GO:0016740 transferase activity 8 GO:0098772 molecular function regulator activity 2 GO:0140110 transcription regulator activity 1
Localization
GO:0005829 cytosol 1
Pathway
R-HSA-1430728 Metabolism 7 R-HSA-392499 Metabolism of proteins 5 R-HSA-5357801 Programmed Cell Death 5 R-HSA-162582 Signal Transduction 3 R-HSA-1640170 Cell Cycle 3 R-HSA-168256 Immune System 3
Partners
BADHIF1AHK2HSF1NLRP3PKM2PRKAA1TSC2

Evidence

Reading pass · 44 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 Pim-2 phosphorylates the BH3 pro-apoptotic protein BAD and maintains rapamycin-resistant phosphorylation of the translational repressor 4E-BP1, thereby promoting cell survival independently of the PI3K/Akt/TOR pathway. Pim-2 also maintained cell size and mitochondrial potential. Constitutive expression in hematopoietic cells, Western blot for phospho-substrates, rapamycin resistance assay, growth factor withdrawal survival assay Genes & development High 12869584
2003 PIM-2 directly phosphorylates BAD on serine 112, and this phosphorylation accounts in part for its ability to reverse BAD-induced cell death. Three PIM-2 protein isoforms are produced in cytokine-treated cells; all three are active kinases, and the short (34 kDa) form is the most active at enhancing survival. In vitro kinase assay, overexpression in FDCP1 cells, Western blot, caspase activation assay The Journal of biological chemistry High 12954615
1995 Pim-2 is 53% identical to Pim-1 at the amino acid level, shares substrate preference and usage of non-AUG initiation codons with Pim-1, and is X-linked. Proviral activation of Pim-2 compensates for loss of Pim-1 in Eµ-myc/Pim-1−/− mice, indicating functional redundancy and placement in the same oncogenic pathway. PCR-based gene identification, proviral tagging in compound mutant mice (complementation tagging genetic epistasis), sequence analysis The EMBO journal High 7781606
2004 Pim-2-mediated cell survival is dependent on NF-κB activation. Pim-2 phosphorylates and activates the kinase Cot, leading to augmented IκB kinase activity and a shift in nuclear NF-κB from p50 homodimers to p50/p65 heterodimers. Blockade of NF-κB eliminates Pim-2-mediated survival, and Pim-2-driven oncogenesis in vivo requires sustained NF-κB activity. Reporter assays for NF-κB activity, co-immunoprecipitation, NF-κB blockade, in vivo lymphoma model, primary cell experiments Cancer research High 15548703
2013 Pim2 directly phosphorylates TSC2 on Ser-1798, relieving TSC2 suppression of mTOR-C1 and thereby promoting MM cell proliferation. TSC2 is identified as a novel Pim2 substrate. shRNA knockdown, selective small-molecule inhibitor, in vitro kinase assay, co-immunoprecipitation, phospho-specific Western blot Blood High 23818547
2009 Crystal structure of PIM2 kinase in complex with an organoruthenium inhibitor was determined, revealing key differences in the ATP-binding site compared with PIM1 that can be exploited for isoform-selective inhibitor design. X-ray crystallography PloS one High 19841674
2018 PIM2 directly binds to hexokinase-2 (HK2) and phosphorylates HK2 on Thr473, increasing HK2 enzyme activity and glycolysis and stabilizing HK2 protein through the chaperone-mediated autophagy (CMA) pathway. This promotes breast cancer cell growth and paclitaxel resistance. Co-immunoprecipitation, in vitro kinase assay, site-directed mutagenesis, glycolysis assay, xenograft mouse model Oncogene High 29985480
2015 Pim-2 kinase phosphorylates the N-terminal domain of Foxp3 at multiple sites, leading to decreased suppressive function of regulatory T cells (Tregs), altered expression of Treg-related proteins, and increased Treg lineage stability. Pharmacological or genetic inhibition of Pim-2 enhances Treg suppressive function. In vitro kinase assay, genetic knockout in murine Treg cells, pharmacological inhibition, DSS-induced colitis model The Journal of biological chemistry High 25987564
2019 PIM2 directly phosphorylates HSF1 at Thr120, disrupting HSF1 binding to the E3 ubiquitin ligase FBXW7 and stabilizing HSF1 protein. Thr120 phosphorylation promotes HSF1 binding to the PD-L1 promoter and enhances PD-L1 expression, driving breast cancer tumorigenesis. In vitro kinase assay, co-immunoprecipitation, site-directed mutagenesis, chromatin immunoprecipitation, xenograft model Cancer research High 31409638
2013 PIM2 binds to and directly phosphorylates pyruvate kinase M2 (PKM2) on Thr-454, increasing PKM2 protein levels and promoting glycolysis (the Warburg effect). The phosphorylation-defective PKM2 mutant shows reduced glycolysis, co-activation of HIF-1α and β-catenin, and increased mitochondrial respiration. Multiple biochemical pulldown/co-IP approaches in vitro and in cells, in vitro kinase assay, phosphorylation-defective mutant analysis, glycolysis assay The Journal of biological chemistry High 24142698
2011 RAG-induced DNA double-strand breaks activate ATM, which induces Pim2 kinase expression in pre-B cells. Pim2 then phosphorylates BAD to promote survival, but unlike IL-7-induced Pim1, Pim2 has antiproliferative functions that prevent pre-B cells with RAG DSBs from entering S phase. Genetic mouse model (ATM deficiency, Pim2 knockout), BAD phosphorylation Western blot, cell cycle analysis, survival assays The Journal of experimental medicine High 22201128
2019 PIM2 binds to AMPKα1 and directly phosphorylates it on Thr467, leading to decreased AMPKα1 kinase activity, which in turn promotes aerobic glycolysis and tumor growth in endometrial cancer. Co-immunoprecipitation, in vitro kinase assay, site-directed mutagenesis, glycolysis assay, xenograft and PIM2 KO mouse models Oncogene High 31358902
2010 Pim-2 phosphorylates the cell cycle inhibitor p21(Cip1/WAF1) on Thr145 in vitro and in vivo, enhancing p21 protein stability and resulting in G1/S cell cycle arrest and inhibition of cell proliferation in HCT116 cells. Pim-2 does not influence nuclear localization of p21 in these cells. In vitro kinase assay, overexpression and siRNA knockdown, Western blot for p21 stability, cell cycle analysis The international journal of biochemistry & cell biology High 20307683
2015 The forkhead transcription factor CHES1/FOXN3 directly binds the PIM2 promoter and represses PIM2 expression. Reduced PIM2 leads to decreased phosphorylation of 4E-BP1, and overexpression of PIM2 or eIF4E partially reverses the antiproliferative effect of CHES1, placing PIM2 downstream of CHES1 in a protein biosynthesis control pathway. Chromatin immunoprecipitation, shRNA knockdown, rescue overexpression, 4E-BP1 phosphorylation Western blot Molecular biology of the cell Medium 24403608
2015 PIM2 promotes persistent STAT3 activation through induction of cytokines, and activated STAT3 in turn increases PIM2 expression, forming a positive feedback loop. This loop drives EMT in breast cancer via ZEB1, and targeting either PIM2, STAT3, or PIM2-dependent cytokines suppresses migratory and invasive properties. Genetic knockdown/overexpression, cytokine neutralization, migration/invasion assays, Western blot Cancer science Medium 25854938
2013 Pim-2 co-expresses with eIF4B in prostate cancer cells and determines the phosphorylation level of eIF4B; higher Pim-2 expression correlates with more eIF4B phosphorylation and lower apoptosis. siRNA knockdown of Pim-2 reduces p-eIF4B and increases apoptosis. siRNA knockdown, transfection overexpression, Western blot for p-eIF4B, apoptosis assay, immunofluorescence co-localization The Prostate Medium 23813671
2009 Pim-2 activates API-5 phosphorylation via the NF-κB pathway to inhibit apoptosis of liver cells; NF-κB inhibition by parthenolide reverses Pim-2-induced API-5 phosphorylation and increases apoptosis. Transfection and siRNA, NF-κB activity assay, Western blot for phospho-API-5, apoptosis analysis with NF-κB inhibitor parthenolide Pathology oncology research Medium 19821157
2011 Pim-2 kinase controls autophagy in chondrocytes: it promotes expression and organization of autophagic proteins LC3 and Beclin-1, enhances lysosomal acidification, and modulates BAD activity. PIM-2-silenced chondrocytes show disrupted autophagic response. These effects are independent of Akt-1. siRNA silencing, immunofluorescence for LC3/Beclin-1, lysosomal acidification assay, rapamycin sensitization, Akt-1 independence controls Journal of cellular physiology Medium 17476689
2013 PIM2 activity is required for phosphorylation of 4E-BP1 and BAD in liver cancer cells, and its kinase activity on these downstream mediators correlates with pro-survival functions. Pim-2 overexpression and knockdown in liver cancer cells, Western blot for phospho-4E-BP1 and phospho-BAD, IL-3 deprivation survival assay The Journal of surgical research Low 18675992
2012 The 34 kDa isoform of PIM-2 (but not the 41 kDa isoform) can, when N-terminally HA-tagged, induce G1 cell cycle arrest and apoptosis in HeLa cells in a kinase-dependent and p73-dependent manner, associated with increased T14/Y15 phosphorylation of CDK2, proteasome-dependent downregulation of CDC25A, and upregulation of p57, E2F-1, and p73. Transient overexpression with isoform-specific and kinase-dead constructs, flow cytometry, dominant-negative p73, p73 siRNA, Western blot PloS one Medium 22506047
2013 PIM-2 expression and activity increase upon UVC radiation in U2OS cells. PIM-2 accelerates removal of UV-induced DNA lesions, reduces γH2AX accumulation, and protects cells through increased E2F-1 and activated ATM levels. Epistasis places PIM-2 upstream of E2F-1 and ATM in the UV-damage response. PIM-2 silencing, overexpression, UV survival assay, γH2AX assay, E2F-1 siRNA, ATM kinase inhibition, DNA lesion removal assay The Journal of biological chemistry Medium 23760264
2017 Pim-2 is identified as a novel RSK2-interacting upstream regulator in FLT3-ITD AML; ectopic RSK2 expression rescues viability of Pim2-depleted cells. Pim2 predominantly controls apoptosis through Bax expression and mitochondrial disruption in FLT3-ITD AML cells. Proteomics/transcriptomics in Pim2-depleted cells, ectopic RSK2 rescue, viability assays, Bax/mitochondria disruption analysis, in vivo mouse model Leukemia Medium 28914261
2016 Pim2 negatively regulates DNA damage response in multiple myeloma: Pim2 knockdown upregulates DDR markers mimicking doxorubicin treatment, placing Pim2 as a negative regulator of the DDR pathway downstream of doxorubicin-DNA binding. Doxorubicin treatment decreases Pim2 levels. shRNA knockdown of Pim2, doxorubicin treatment, Western blot for DDR markers, overexpression survival assay Blood cancer journal Medium 27564460
2015 All three Pim2 isoforms localize to the cytoplasm in leukemic cells and are degraded by the proteasome without detectable ubiquitination—purified 20S proteasome particles degrade Pim2 in vitro. Pim2 mRNA accumulation is controlled by erythropoietin via STAT5; translation is not regulated by mTORC1. Subcellular fractionation, proteasome inhibitors (half-life analysis), E1 inhibitor Pyr41, in vitro 20S proteasome degradation assay, STAT5 inhibition, signaling pathway inhibitors Bioscience reports High 26500282
2018 PIM2 directly binds tristetraprolin (TTP) and promotes its proteasomal degradation independently of PIM2 kinase activity, thereby de-repressing TTP-mediated inhibition of breast cancer cell proliferation and migration. Co-immunoprecipitation, kinase-dead PIM2 mutant, ubiquitin-proteasome pathway assays, immunohistochemistry correlation, in vivo xenograft Molecular oncology Medium 29570932
2014 PIM2 inhibition reduces phosphorylation of 4E-BP1 (Thr37/46 and Ser65), establishing p4E-BP1 as a molecular biomarker of PIM2 kinase activity and indicating PIM2 involvement in regulating mTORC1. Pharmacological inhibition and genetic knockdown of PIM2, Western blot for phospho-4E-BP1, lymphoma cell lines Blood Medium 21937691
2019 In CML stem cells (CMLSCs), PIM2 expression is maintained by both a BCR-ABL-dependent STAT5-mediated pathway and a BCR-ABL-independent STAT4-mediated pathway. PIM2 phosphorylates and inhibits BAD, contributing to imatinib resistance in CMLSCs. Single-cell RNA-seq, BCR-ABL identification, STAT4/STAT5 pathway analysis, BAD phosphorylation Western blot, mouse CML model, PIM inhibitor combined treatment PNAS Medium 31068472
2016 Pim-2 regulates osteoblastogenesis negatively; enforced expression abrogates BMP-2-induced osteoblastogenesis while Pim-2 inhibition or siRNA restores osteoblastogenesis. The inhibitor SMI-16a potentiates BMP-2 anabolic signaling while suppressing TGF-β signaling. siRNA knockdown, overexpression, SMI-16a inhibitor treatment, BMP-2-induced osteoblastogenesis assay, TGF-β/BMP signaling Western blot, in vivo MM animal model Leukemia Medium 24787487
2016 PIM2 kinase sustains G1/S transition during plasmablast generation by acting on CDC25A and p27Kip1, and hinders caspase 3-driven apoptosis through BAD phosphorylation and cytoplasmic stabilization of p21Cip1. Morpholino antisense inhibition, pharmacological PIM inhibition, Western blot for CDC25A/p27Kip1/BAD phosphorylation/p21Cip1, flow cytometry for cell cycle and apoptosis Blood High 35108359
2021 PIM2 directly phosphorylates PFKFB3 at Ser478, enhancing PFKFB3 protein stability through the ubiquitin-proteasome pathway, which promotes glycolysis, BC cell growth, and paclitaxel resistance. Mass spectrometry, co-immunoprecipitation, in vitro kinase assay, PFKFB3 site-specific mutants, ubiquitination assay, xenograft model Clinical and translational medicine High 33931981
2022 PIM2 directly phosphorylates PFKFB4 on Thr140 and enhances PFKFB4 protein expression through the ubiquitin-proteasome pathway, promoting glycolysis and cell growth in endometriosis. Co-immunoprecipitation, in vitro kinase assay, site-directed mutagenesis, ubiquitin-proteasome assay, in vivo endometriosis model Cell death & disease High 36109523
2016 PIM-2 isoform negatively regulates T cell responses to alloantigen (unlike PIM-1 and PIM-3, which are positive regulators); PIM-2-deficient T cells show increased Th1 differentiation, proliferation, and migration, leading to accelerated GVHD; PIM-2 also suppresses CD8+ T cell antitumor responses. Pim-2 genetic knockout mice, allogeneic bone marrow transplantation model, syngeneic tumor rejection model, adoptive T cell transfer, flow cytometry, rescue expression experiments The Journal of clinical investigation High 29781812
2019 TRAF3 deficiency induces Pim2 upregulation in B cells via STAT3 (independent of NF-κB2), and elevated Pim2 in turn increases c-Myc protein levels with reduced c-Myc ubiquitination. TRAF3 knockout B cells, STAT3 inhibition, Pim inhibitor treatment, c-Myc ubiquitination assay, Western blot Scientific reports Medium 31501481
2016 PIM2 kinase phosphorylates the serine/threonine kinase Bim on Ser65, promotes its proteasomal degradation, and protects H9c2 cardiomyocytes from hypoxia/reoxygenation-induced apoptosis. A Bim S65A mutation reverses the anti-apoptotic role of Pim-2. Co-immunoprecipitation (Pim-2/Bim interaction), site-directed mutagenesis (Bim S65A), proteasome inhibitor MG132, overexpression and siRNA, Western blot for Cyt C Environmental toxicology and pharmacology Medium 27770661
2017 PIM2 directly phosphorylates PGK1 at Ser203, PDHA1 at Ser300, and PFKFB2 at Ser466, promoting glycolytic reprogramming during M1 macrophage polarization and inflammatory arthritis. Conditional macrophage-specific Pim2 knockout, in vitro kinase assays (implied by direct phosphorylation claim and biochemical analyses), glycolytic assays, CIA arthritis model Cellular & molecular immunology Medium 40000906
2020 PIM2 activates NF-κB signaling in hepatocellular carcinoma by upregulating phosphorylation of RIPK2. TNFα induces PIM2 expression, and PIM2 in turn upregulates TNFα, forming a positive feedback loop. Functional studies with overexpression/knockdown, Western blot for phospho-RIPK2, NF-κB reporter, TNFα stimulation experiments, in vivo xenograft Cell death & disease Medium 32641749
2020 PIM2 directly interacts with NLRP3 and promotes LPS-triggered NLRP3 inflammasome activation (Caspase-1, IL-1β) in macrophages; Pim2 knockout significantly alleviated ARDS in LPS-challenged mice. Co-immunoprecipitation, PIM2 overexpression and knockdown, Pim2 knockout mice, ARDS mouse model, inflammasome component Western blot Biochemical and biophysical research communications Medium 33333710
2020 PIM2 phosphorylates FBP1 on Ser144, abrogating FBP1 interaction with NF-κB p65 and promoting p65 stability through the CHIP-mediated proteasome pathway, leading to increased PD-L1 expression and breast tumor growth. Immunoaffinity purification, co-immunoprecipitation, in vitro kinase assay, ubiquitination/proteasome assay, PIM2 KO mice, in vivo xenograft Theranostics High 32754266
2014 A regulatory feedback loop exists between HIF-1α and PIM2: HIF-1α induces PIM2 expression by binding hypoxia-responsive elements (HREs) in the PIM2 promoter, and PIM2 in turn interacts with HIF-1α (at its transactivation domain) as a co-factor (not a kinase) to enhance HIF-1α transcriptional activity. ChIP for HRE binding, co-immunoprecipitation of PIM2/HIF-1α, domain-mapping, glucose metabolism assay, hypoxia experiments PloS one Medium 24505470
2022 PIM2 inhibition reduces phosphorylated BAD production and activates ISR-mediated NOXA expression, shifting plasma cells to MCL1 dependence. Combined PIM/MCL1 inhibition synergistically controls tumor growth, and ISR-specific inhibition reverses this synergy. PIM2 inhibition, MCL1 inhibitor, ISR inhibitor (genetic and pharmacological), Western blot for phospho-BAD and NOXA, xenograft mouse model Nature communications Medium 39747141
2017 PIM2 regulates stemness in embryonic stem cells by directly phosphorylating 4E-BP1, leading to eIF4E release and facilitated translation of pluripotent genes. Pim2 knockout inhibits ESC self-renewal and differentiation capability. Pim2 knockout, in vitro kinase assay for 4E-BP1 phosphorylation, eIF4E cap-binding assay, self-renewal and differentiation assays Science bulletin Medium 36659438
2024 PIM2 phosphorylates USP27X, promoting USP27X deubiquitylase activity toward MYC, thereby stabilizing MYC protein and increasing HK2-mediated aerobic glycolysis in breast cancer. This PIM2-USP27X-MYC axis is validated in PIM2-knockout mice. Co-immunoprecipitation, in vitro kinase assay, deubiquitylation assay, MYC stability Western blot, glycolysis assay, PIM2 KO mouse model Oncogene High 38969771
2022 Pim-2 regulates osteoclastic bone resorption activity by controlling expression of the V-ATPase a3 isoform; Pim-2 siRNA silencing diminishes RANKL-induced resorptive activity and attenuates RANKL-triggered a3 stimulation without affecting osteoclast differentiation. Pim-2 overexpression stimulates a3 subunit expression and induces bone resorption. siRNA silencing and retroviral overexpression in BMMs, RANKL-induced osteoclastogenesis, dentin bone resorption assay, RT-PCR/Western blot for a3 isoform Journal of cellular physiology Medium 35696529
2018 p53 activation (via actinomycin D + nutlin-3a) leads to accumulation of PIM2 in a p53-dependent manner (abrogated by p53 knockdown), which then phosphorylates BAD on Ser136, providing an inactivating (pro-survival) signal concurrent with p53-induced apoptosis. Antibody arrays for apoptotic proteins, Western blot for phospho-BAD, p53 knockdown, A549 cells Archives of biochemistry and biophysics Medium 30096294

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 The serine/threonine kinase Pim-2 is a transcriptionally regulated apoptotic inhibitor. Genes & development 282 12869584
2003 The PIM-2 kinase phosphorylates BAD on serine 112 and reverses BAD-induced cell death. The Journal of biological chemistry 236 12954615
1995 Proviral tagging in E mu-myc transgenic mice lacking the Pim-1 proto-oncogene leads to compensatory activation of Pim-2. The EMBO journal 167 7781606
2009 Synthesis and evaluation of novel inhibitors of Pim-1 and Pim-2 protein kinases. Journal of medicinal chemistry 148 19072652
2013 Pim2 is required for maintaining multiple myeloma cell growth through modulating TSC2 phosphorylation. Blood 138 23818547
1997 Pim-2 transgene induces lymphoid tumors, exhibiting potent synergy with c-myc. Oncogene 138 9294606
2018 PIM2-mediated phosphorylation of hexokinase 2 is critical for tumor growth and paclitaxel resistance in breast cancer. Oncogene 114 29985480
2011 The serine/threonine kinase Pim-2 is a novel anti-apoptotic mediator in myeloma cells. Leukemia 96 21475253
1989 Evidence for the involvement of pim-2, a new common proviral insertion site, in progression of lymphomas. The EMBO journal 93 2721500
2011 PIM2 inhibition as a rational therapeutic approach in B-cell lymphoma. Blood 91 21937691
2012 Discovery of novel benzylidene-1,3-thiazolidine-2,4-diones as potent and selective inhibitors of the PIM-1, PIM-2, and PIM-3 protein kinases. Bioorganic & medicinal chemistry letters 83 22727640
2004 Lymphocyte transformation by Pim-2 is dependent on nuclear factor-kappaB activation. Cancer research 82 15548703
2013 Proviral insertion in murine lymphomas 2 (PIM2) oncogene phosphorylates pyruvate kinase M2 (PKM2) and promotes glycolysis in cancer cells. The Journal of biological chemistry 77 24142698
2015 Pim-2 Kinase Influences Regulatory T Cell Function and Stability by Mediating Foxp3 Protein N-terminal Phosphorylation. The Journal of biological chemistry 76 25987564
2019 Phosphorylation of HSF1 by PIM2 Induces PD-L1 Expression and Promotes Tumor Growth in Breast Cancer. Cancer research 75 31409638
2009 Crystal structure of the PIM2 kinase in complex with an organoruthenium inhibitor. PloS one 72 19841674
2007 Pim-1 and Pim-2 kinases are required for efficient pre-B-cell transformation by v-Abl oncogene. Blood 66 18042805
2005 Pim-2 upregulation: biological implications associated with disease progression and perinueral invasion in prostate cancer. The Prostate 66 16015593
2014 PIM kinases are essential for chronic lymphocytic leukemia cell survival (PIM2/3) and CXCR4-mediated microenvironmental interactions (PIM1). Molecular cancer therapeutics 59 24659821
2014 Pim-2 kinase is an important target of treatment for tumor progression and bone loss in myeloma. Leukemia 55 24787487
2021 Positive regulation of PFKFB3 by PIM2 promotes glycolysis and paclitaxel resistance in breast cancer. Clinical and translational medicine 54 33931981
2008 Isoxazolo[3,4-b]quinoline-3,4(1H,9H)-diones as unique, potent and selective inhibitors for Pim-1 and Pim-2 kinases: chemistry, biological activities, and molecular modeling. Bioorganic & medicinal chemistry letters 50 18790640
2009 PIM2 Induced COX-2 and MMP-9 expression in macrophages requires PI3K and Notch1 signaling. PloS one 49 19290049
2022 Phosphorylation of PFKFB4 by PIM2 promotes anaerobic glycolysis and cell proliferation in endometriosis. Cell death & disease 44 36109523
2011 RAG-induced DNA double-strand breaks signal through Pim2 to promote pre-B cell survival and limit proliferation. The Journal of experimental medicine 43 22201128
2015 Persistent activation of STAT3 by PIM2-driven positive feedback loop for epithelial-mesenchymal transition in breast cancer. Cancer science 42 25854938
2011 Discovery of novel 3,5-disubstituted indole derivatives as potent inhibitors of Pim-1, Pim-2, and Pim-3 protein kinases. Bioorganic & medicinal chemistry letters 40 21945284
2009 Pim-2 activates API-5 to inhibit the apoptosis of hepatocellular carcinoma cells through NF-kappaB pathway. Pathology oncology research : POR 40 19821157
2019 Negative regulation of AMPKα1 by PIM2 promotes aerobic glycolysis and tumorigenesis in endometrial cancer. Oncogene 38 31358902
1998 The human Pim-2 proto-oncogene and its testicular expression. Biochimica et biophysica acta 37 9804974
2016 Novel inhibition of PIM2 kinase has significant anti-tumor efficacy in multiple myeloma. Leukemia 36 28008178
2014 CHES1/FOXN3 regulates cell proliferation by repressing PIM2 and protein biosynthesis. Molecular biology of the cell 35 24403608
2010 Pim-2 phosphorylation of p21(Cip1/WAF1) enhances its stability and inhibits cell proliferation in HCT116 cells. The international journal of biochemistry & cell biology 35 20307683
2016 The role of PIM1/PIM2 kinases in tumors of the male reproductive system. Scientific reports 34 27901106
2021 Protein kinase PIM2: A simple PIM family kinase with complex functions in cancer metabolism and therapeutics. Journal of Cancer 33 33854618
2018 PIM-2 protein kinase negatively regulates T cell responses in transplantation and tumor immunity. The Journal of clinical investigation 33 29781812
2008 Serine/threonine kinase Pim-2 promotes liver tumorigenesis induction through mediating survival and preventing apoptosis of liver cell. The Journal of surgical research 33 18675992
2007 PIM-2 is an independent regulator of chondrocyte survival and autophagy in the epiphyseal growth plate. Journal of cellular physiology 33 17476689
2025 Targeting macrophage polarization by inhibiting Pim2 alleviates inflammatory arthritis via metabolic reprogramming. Cellular & molecular immunology 31 40000906
2020 PIM2 promotes hepatocellular carcinoma tumorigenesis and progression through activating NF-κB signaling pathway. Cell death & disease 31 32641749
2011 Antimyeloma activity of the sesquiterpene lactone cnicin: impact on Pim-2 kinase as a novel therapeutic target. Journal of molecular medicine (Berlin, Germany) 29 22205266
2017 RSK2 is a new Pim2 target with pro-survival functions in FLT3-ITD-positive acute myeloid leukemia. Leukemia 28 28914261
2007 Pim2 complements Flt3 wild-type receptor in hematopoietic progenitor cell transformation. Leukemia 28 17943165
2015 Loss of PIM2 enhances the anti-proliferative effect of the pan-PIM kinase inhibitor AZD1208 in non-Hodgkin lymphomas. Molecular cancer 26 26643319
2021 Long non-coding RNA SOX21-AS1 modulates lung cancer progress upon microRNA miR-24-3p/PIM2 axis. Bioengineered 25 34511042
2018 PIM2 interacts with tristetraprolin and promotes breast cancer tumorigenesis. Molecular oncology 25 29570932
2015 Pim-2 Modulates Aerobic Glycolysis and Energy Production during the Development of Colorectal Tumors. International journal of medical sciences 25 26078709
2018 MicroRNA-26b-5p enhances T cell responses by targeting PIM-2 in hepatocellular carcinoma. Cellular signalling 24 30593845
2017 Inflammation and stem markers association to PIM1/PIM2 kinase-induced tumors in breast and uterus. Oncotarget 24 28938604
2014 PIM2 kinase is induced by cisplatin in ovarian cancer cells and limits drug efficacy. Journal of proteome research 24 25099161
2015 Control of Pim2 kinase stability and expression in transformed human haematopoietic cells. Bioscience reports 23 26500282
2022 PIM2 Expression Induced by Proinflammatory Macrophages Suppresses Immunotherapy Efficacy in Hepatocellular Carcinoma. Cancer research 22 35802648
2013 The over-expression of Pim-2 promote the tumorigenesis of prostatic carcinoma through phosphorylating eIF4B. The Prostate 22 23813671
2020 Fructose-1, 6-bisphosphatase 1 interacts with NF-κB p65 to regulate breast tumorigenesis via PIM2 induced phosphorylation. Theranostics 21 32754266
2014 A regulatory feedback loop between HIF-1α and PIM2 in HepG2 cells. PloS one 21 24505470
2023 PIM2 Promotes the Development of Ovarian Endometriosis by Enhancing Glycolysis and Fibrosis. Reproductive sciences (Thousand Oaks, Calif.) 20 37059967
2016 Pim2 is important for regulating DNA damage response in multiple myeloma cells. Blood cancer journal 20 27564460
2012 Activation of cell cycle arrest and apoptosis by the proto-oncogene Pim-2. PloS one 20 22506047
2009 SOCS3 expression induced by PIM2 requires PKC and PI3K signaling. Molecular immunology 20 19608279
2021 Abrine promotes cell proliferation and inhibits apoptosis of interleukin-1β-stimulated chondrocytes via PIM2/VEGF signalling in osteoarthritis. Phytomedicine : international journal of phytotherapy and phytopharmacology 19 35026522
2019 Inhibition of PIM2 in liver cancer decreases tumor cell proliferation in vitro and in vivo primarily through the modulation of cell cycle progression. International journal of oncology 19 31894300
2018 Downregulation of Pim-2 induces cell cycle arrest in the G0/G1 phase via the p53-non-dependent p21 signaling pathway. Oncology letters 18 29541172
2022 PIM2 kinase has a pivotal role in plasmablast generation and plasma cell survival, opening up novel treatment options in myeloma. Blood 17 35108359
2019 TRAF3 regulates the oncogenic proteins Pim2 and c-Myc to restrain survival in normal and malignant B cells. Scientific reports 17 31501481
2013 The PIM-2 kinase is an essential component of the ultraviolet damage response that acts upstream to E2F-1 and ATM. The Journal of biological chemistry 15 23760264
2017 Pim-2 Cooperates with Downstream Factor XIAP to Inhibit Apoptosis and Intensify Malignant Grade in Prostate Cancer. Pathology oncology research : POR 14 29124675
2019 Prosurvival kinase PIM2 is a therapeutic target for eradication of chronic myeloid leukemia stem cells. Proceedings of the National Academy of Sciences of the United States of America 12 31068472
2021 Myeloma-Bone Interaction: A Vicious Cycle via TAK1-PIM2 Signaling. Cancers 11 34503251
2016 Characterization of HJ-PI01 as a novel Pim-2 inhibitor that induces apoptosis and autophagic cell death in triple-negative human breast cancer. Acta pharmacologica Sinica 11 27397540
2010 Pim2 cooperates with PML-RARalpha to induce acute myeloid leukemia in a bone marrow transplantation model. Blood 11 20215640
2017 Role of PIM2 in allergic asthma. Molecular medicine reports 10 28944837
2020 PIM2 deletion alleviates lipopolysaccharide (LPS)-induced respiratory distress syndrome (ARDS) by suppressing NLRP3 inflammasome. Biochemical and biophysical research communications 9 33333710
2018 Computer aided drug design based on 3D-QSAR and molecular docking studies of 5-(1H-indol-5-yl)-1,3,4-thiadiazol-2-amine derivatives as PIM2 inhibitors: a proposal to chemists. In silico pharmacology 9 30607318
2016 Pim-2 protects H9c2 cardiomyocytes from hypoxia/reoxygenation-induced apoptosis via downregulation of Bim expression. Environmental toxicology and pharmacology 9 27770661
2015 Effects of low doses of Tat-PIM2 protein against hippocampal neuronal cell survival. Journal of the neurological sciences 8 26365288
2012 Inhibition of Pim2-prolonged skin allograft survival through the apoptosis regulation pathway. Cellular & molecular immunology 8 23085945
2010 Ectopic over-expression of oncogene Pim-2 induce malignant transformation of nontumorous human liver cell line L02. Journal of Korean medical science 8 20592892
2021 Pim-2 kinase inhibits inflammation by suppressing the mTORC1 pathway in atherosclerosis. Aging 7 34547720
2005 Antisense oligodeoxynucleotides targeting the serine/threonine kinase Pim-2 inhibited proliferation of DU-145 cells. Acta pharmacologica Sinica 7 15715935
2024 Phosphorylation of USP27X by PIM2 promotes glycolysis and breast cancer progression via deubiquitylation of MYC. Oncogene 6 38969771
2021 Engineered Fully Human Single-Chain Monoclonal Antibodies to PIM2 Kinase. Molecules (Basel, Switzerland) 6 34770845
2017 Upregulation of PIM2 by Underexpression of MicroRNA-135-5p Improves Survival Rates of Skin Allografts by Suppressing Apoptosis of Fibroblast Cells. Medical science monitor : international medical journal of experimental and clinical research 6 28064305
2022 Pim-2 Kinase Regulates Energy Metabolism in Multiple Myeloma. Cancers 5 36612063
2021 Inhibition of Pim-2 kinase by LT-171-861 promotes DNA damage and exhibits enhanced lethal effects with PARP inhibitor in multiple myeloma. Biochemical pharmacology 5 34111425
2019 Expression of the PIM2 gene is associated with more aggressive clinical course in patients with chronic lymphocytic leukemia. Advances in clinical and experimental medicine : official organ Wroclaw Medical University 5 30525315
2012 MYC and PIM2 co-expression in mouse bone marrow cells readily establishes permanent myeloid cell lines that can induce lethal myeloid sarcoma in vivo. Molecules and cells 5 22843119
2025 PIM2 inhibition promotes MCL1 dependency in plasma cells involving integrated stress response-driven NOXA expression. Nature communications 4 39747141
2024 Acute accumulation of PIM2 and NRF2 and recovery of β5 subunit activity mitigate multiple myeloma cell susceptibility to proteasome inhibitors. International journal of hematology 4 38245883
2023 Final step of B-cell differentiation into plasmablasts; the right time to activate plasma cell PIM2 kinase. Immunology letters 4 37207916
2022 Targeting PIM2 by JP11646 results in significant antitumor effects in solid tumors. International journal of oncology 4 35920189
2019 High expression of PIM2 induces HSC proliferation in myelodysplastic syndromes via the IDH1/HIF1-α signaling pathway. Oncology letters 4 31186757
2018 PIM2 survival kinase is upregulated in a p53-dependent manner in cells treated with camptothecin or co-treated with actinomycin D and nutlin-3a. Archives of biochemistry and biophysics 4 30096294
2017 PIM2 regulates stemness through phosphorylation of 4E-BP1. Science bulletin 4 36659438
2007 Pim2 inhibitors from the Papua New Guinean plant Cupaniopsis macropetala. Journal of natural products 4 18163587
2025 Colchicine alleviates atherosclerosis combined with diabetes mellitus by targeting PIM2 and regulating the NF-κB signaling pathway. Phytomedicine : international journal of phytotherapy and phytopharmacology 3 40865347
2024 Regnase-1 D141N mutation induces CD4+ T cell-mediated lung granuloma formation via upregulation of Pim2. International immunology 3 38700370
2022 Pim-2 regulates bone resorptive activity of osteoclasts via V-ATPase a3 isoform expression in periodontal disease. Journal of cellular physiology 3 35696529
2023 Protective effects of cell permeable Tat-PIM2 protein on oxidative stress induced dopaminergic neuronal cell death. Heliyon 2 37223703
2025 Combining PIM-2 and PARP1 Inhibitors Induces MICA Expression on Multiple Myeloma Cells to Activate NK Cells through NKG2D Binding. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 1 40557764
2024 Identification and assessment of new PIM2 inhibitors for treating hematologic cancers: A combined approach of energy-based virtual screening and machine learning evaluation. Archiv der Pharmazie 1 38263717

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