Affinage

PIM2

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

Length
311 aa
Mass
34.2 kDa
Annotated
2026-04-28
100 papers in source corpus 39 papers cited in narrative 39 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PIM2 is a constitutively active serine/threonine kinase that promotes cell survival, metabolic reprogramming, and proliferation across hematopoietic and solid-tumor contexts. It phosphorylates the pro-apoptotic protein BAD on Ser112 to block apoptosis, maintains rapamycin-resistant phosphorylation of the translational repressor 4E-BP1 independently of PI3K/Akt/mTOR, and phosphorylates TSC2 on Ser1798 to relieve mTORC1 suppression (PMID:12954615, PMID:12869584, PMID:23818547). PIM2 is a central driver of the Warburg effect through direct phosphorylation of multiple glycolytic regulators — HK2 (Thr473), PKM2 (Thr454), PFKFB3 (Ser478), PFKFB4 (Thr140), AMPKα1 (Thr467), PGK1 (Ser203), PDHA1 (Ser300), and PFKFB2 (Ser466) — stabilizing several of these substrates against proteasomal or CMA-mediated degradation (PMID:29985480, PMID:24142698, PMID:33931981, PMID:31358902, PMID:40000906). PIM2 also modulates immune responses by phosphorylating Foxp3 to reduce regulatory T cell suppressive function, stabilizing HSF1 (Thr120) to drive PD-L1 expression, promoting NF-κB activation via Cot phosphorylation and FBP1 (Ser144) phosphorylation, and regulating NLRP3 inflammasome activation in macrophages (PMID:25987564, PMID:31409638, PMID:15548703, PMID:32754266, PMID:33333710).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 1995 High

    Identification of PIM2 as a second PIM family member that functionally compensates for PIM1 in Myc-driven lymphomagenesis established that PIM kinases act as redundant oncogenic collaborators with Myc.

    Evidence Proviral tagging screen in Eμ-myc/Pim1−/− mice with sequence analysis

    PMID:7781606

    Open questions at the time
    • Substrate specificity differences between PIM1 and PIM2 not resolved
    • Mechanism of oncogenic cooperation with Myc unknown
  2. 2003 High

    Direct identification of BAD Ser112 and 4E-BP1 as PIM2 substrates established two parallel survival mechanisms — apoptosis suppression and cap-dependent translation maintenance — operating independently of PI3K/Akt/mTOR.

    Evidence In vitro kinase assays, rapamycin-resistant 4E-BP1 phosphorylation, FDCP1 overexpression rescue

    PMID:12869584 PMID:12954615

    Open questions at the time
    • Direct phosphorylation site on 4E-BP1 not mapped in these studies
    • Whether PIM2-4E-BP1 axis operates in non-hematopoietic cells unclear
  3. 2004 High

    Demonstration that PIM2 activates NF-κB via Cot kinase phosphorylation, shifting nuclear NF-κB from p50 homodimers to transcriptionally active p50/p65 heterodimers, revealed a second pro-survival signaling axis distinct from BAD/4E-BP1.

    Evidence Dominant-negative constructs, NF-κB reporters, Co-IP, in vivo lymphoma model

    PMID:15548703

    Open questions at the time
    • Direct phosphorylation site on Cot not mapped
    • Whether NF-κB activation is required in all PIM2-driven cancers unknown
  4. 2007 Medium

    PIM2 was linked to autophagy regulation through modulation of LC3, Beclin-1, and lysosomal acidification in chondrocytes, extending PIM2 function beyond apoptosis into alternative survival mechanisms.

    Evidence siRNA knockdown with autophagy marker and lysosomal assays in epiphyseal chondrocytes

    PMID:17476689

    Open questions at the time
    • Direct PIM2 substrates in autophagy pathway not identified
    • Confirmation in other cell types lacking
  5. 2009 High

    The crystal structure of PIM2 with an organoruthenium inhibitor defined the ATP-binding site architecture and isoform-specific features distinguishing PIM2 from PIM1, enabling rational inhibitor design.

    Evidence X-ray crystallography of PIM2-inhibitor complex

    PMID:19841674

    Open questions at the time
    • No structures with physiological substrates
    • Structural basis for constitutive activity not fully elucidated
  6. 2010 High

    Identification of p21Cip1 Thr145 as a PIM2 phosphosite that stabilizes p21 and induces G1/S arrest demonstrated that PIM2 can exert antiproliferative effects depending on context, complicating its purely oncogenic image.

    Evidence In vitro kinase assay with in vivo phosphorylation confirmation, cell cycle analysis in HCT116

    PMID:20307683

    Open questions at the time
    • How PIM2 switches between pro-proliferative and antiproliferative outputs unclear
    • Isoform-specific effects not resolved
  7. 2011 High

    Placing PIM2 downstream of RAG-induced DNA breaks and ATM signaling in pre-B cells revealed a physiological non-oncogenic role: PIM2 promotes survival of cells undergoing V(D)J recombination via BAD phosphorylation.

    Evidence Genetic epistasis with RAG-deficient and ATM-deficient mouse models, retroviral expression

    PMID:22201128

    Open questions at the time
    • Direct ATM-PIM2 signaling intermediates not identified
    • Relative contributions of PIM2 vs PIM1 in pre-B cell survival not quantified
  8. 2013 High

    Direct phosphorylation of TSC2 (Ser1798) and PKM2 (Thr454) established PIM2 as a node connecting mTORC1 activation to metabolic reprogramming (Warburg effect), expanding the substrate repertoire from apoptosis regulators to metabolic enzymes.

    Evidence In vitro kinase assays with site-directed mutagenesis, metabolic flux assays, mTOR-C1 activity readouts in myeloma and cancer cells

    PMID:23818547 PMID:24142698

    Open questions at the time
    • Whether TSC2 and PKM2 phosphorylation events are coordinated or independent unclear
    • Quantitative contribution of PIM2 vs PI3K/Akt to mTORC1 not resolved
  9. 2013 Medium

    PIM2 was placed upstream of E2F-1 and ATM in the UV damage response, suggesting a kinase-dependent role in DNA repair beyond its established survival functions.

    Evidence Overexpression/knockdown with UV irradiation, γH2AX quantification, ATM inhibitor epistasis

    PMID:23760264

    Open questions at the time
    • Direct PIM2 substrate in DNA repair pathway not identified
    • Not independently replicated
    • Mechanism linking PIM2 to ATM activation unknown
  10. 2014 Medium

    Discovery that PIM2 interacts with HIF-1α as a transcriptional co-factor (not upstream kinase) in a positive feedback loop revealed a kinase-independent mechanism by which PIM2 enhances hypoxic gene expression.

    Evidence Co-IP, HRE reporter, ChIP showing HIF-1α binds PIM2 promoter HREs

    PMID:24505470

    Open questions at the time
    • Structural basis of PIM2–HIF-1α interaction unknown
    • Whether co-factor role is truly kinase-independent not confirmed with kinase-dead mutant in this study
  11. 2015 High

    Phosphorylation of Foxp3 by PIM2 was shown to decrease Treg suppressive function, establishing PIM2 as a negative regulator of immune tolerance and a therapeutic target for enhancing Treg activity.

    Evidence In vitro kinase assay, Pim2 genetic knockout Tregs, PIM inhibitor, DSS colitis model

    PMID:25987564

    Open questions at the time
    • Specific Foxp3 phosphosites mediating functional suppression not fully mapped
    • Whether PIM2 inhibition boosts Treg function in human disease unknown
  12. 2015 Medium

    Characterization of PIM2 protein turnover showed ubiquitination-independent degradation by the 20S proteasome for all three isoforms, with transcriptional regulation via STAT5 (erythropoietin) and repression by FOXN3, establishing that PIM2 activity is controlled primarily at expression level.

    Evidence In vitro 20S proteasome degradation assay, E1 inhibitor (Pyr41), STAT5 inhibition, ChIP for FOXN3 on PIM2 promoter

    PMID:24403608 PMID:26500282

    Open questions at the time
    • Whether other E3-independent proteasomal pathways contribute in vivo unclear
    • Full repertoire of transcriptional regulators of PIM2 not catalogued
  13. 2018 High

    Direct phosphorylation of HK2 on Thr473 by PIM2, stabilizing HK2 via the CMA pathway and driving glycolysis, solidified PIM2 as a master regulator of glycolytic enzyme stability in cancer.

    Evidence Co-IP, in vitro kinase assay, CMA pathway analysis, breast cancer xenograft models

    PMID:29985480

    Open questions at the time
    • Whether PIM2 phosphorylation of HK2 occurs in non-cancer contexts unknown
    • Structural basis for CMA evasion upon phosphorylation not determined
  14. 2018 Medium

    PIM2 was shown to promote TTP (tristetraprolin) degradation independently of its kinase activity, revealing a scaffolding function that regulates mRNA stability programs in breast cancer.

    Evidence Co-IP, kinase-dead mutant analysis, ubiquitination assay, xenograft

    PMID:29570932

    Open questions at the time
    • E3 ligase recruited by PIM2 for TTP ubiquitination not identified
    • Single lab finding not independently confirmed
  15. 2019 High

    Identification of HSF1 Thr120 and AMPKα1 Thr467 as PIM2 phosphosites linked PIM2 to immune evasion (PD-L1 upregulation via HSF1) and metabolic control (AMPK inactivation promoting glycolysis), broadening the substrate repertoire to immune checkpoint and energy-sensing pathways.

    Evidence In vitro kinase assays, site-directed mutagenesis, ChIP for HSF1 on PD-L1 promoter, metabolic assays, in vivo models

    PMID:31358902 PMID:31409638

    Open questions at the time
    • Whether HSF1 phosphorylation by PIM2 affects heat shock response per se not tested
    • Relative contribution of PIM2 vs other kinases to AMPK inactivation not quantified
  16. 2019 High

    In CML stem cells, a BCR-ABL-independent STAT4-mediated pathway was shown to sustain PIM2 expression and BAD phosphorylation, explaining imatinib resistance and providing rationale for combined PIM/TKI therapy.

    Evidence Single-cell RNA-seq, genetic dissection of STAT4/STAT5 pathways, combined inhibitor treatment in mouse CML model

    PMID:31068472

    Open questions at the time
    • Whether STAT4-PIM2 axis operates in other resistant cancers unknown
    • Direct STAT4 binding to PIM2 promoter not demonstrated
  17. 2020 High

    Phosphorylation of FBP1 on Ser144 by PIM2 was shown to disrupt FBP1–NF-κB p65 interaction, stabilizing p65 and upregulating PD-L1 transcription, revealing a second PIM2-driven immune evasion mechanism converging on PD-L1.

    Evidence In vitro kinase assay, Co-IP, ubiquitination assay, PIM2-KO mice, tumor models

    PMID:32754266

    Open questions at the time
    • Whether FBP1 phosphorylation affects its metabolic (gluconeogenic) function simultaneously unknown
    • Relative importance of HSF1 vs FBP1/NF-κB routes to PD-L1 not compared
  18. 2021 High

    PFKFB3 Ser478 phosphorylation by PIM2, stabilizing PFKFB3 against proteasomal degradation, extended the pattern of PIM2-mediated glycolytic enzyme stabilization to a key allosteric activator of glycolysis.

    Evidence Mass spectrometry, in vitro kinase assay, phosphosite mutagenesis, ubiquitination assay, in vivo breast cancer models

    PMID:33931981

    Open questions at the time
    • Whether PFKFB3 phosphorylation affects its nuclear functions not tested
  19. 2022 Medium

    PIM2 was linked to NLRP3 inflammasome activation in macrophages and osteoclast resorptive activity via V-ATPase a3 regulation, expanding PIM2 biology into innate immunity and bone remodeling.

    Evidence Co-IP for NLRP3 interaction, PIM2-KO ARDS model; siRNA/overexpression with RANKL-induced osteoclast assays

    PMID:33333710 PMID:35696529

    Open questions at the time
    • Direct PIM2 phosphorylation site on NLRP3 not mapped
    • Mechanism connecting PIM2 to V-ATPase a3 expression not established
    • Independent replication needed for both findings
  20. 2024 High

    Phosphorylation of USP27X by PIM2 was shown to enhance its deubiquitylase activity toward MYC, stabilizing MYC protein and driving HK2-dependent glycolysis, thereby connecting PIM2 to post-translational MYC regulation.

    Evidence In vitro kinase assay, deubiquitylation assay, MYC stability analysis, PIM2-KO mice

    PMID:38969771

    Open questions at the time
    • Specific USP27X phosphosite not reported in the discovery
    • Whether PIM2-USP27X-MYC axis operates in non-breast cancers not tested
  21. 2025 High

    Identification of PGK1, PDHA1, and PFKFB2 as direct PIM2 substrates in M1 macrophages, with conditional knockout attenuating arthritis, positioned PIM2 as a central glycolytic switch during inflammatory macrophage polarization.

    Evidence In vitro kinase assays with site-specific phosphorylation, macrophage-specific conditional KO, CIA model

    PMID:40000906

    Open questions at the time
    • Whether PIM2-driven glycolytic reprogramming is specific to M1 or also affects M2 macrophages not resolved
    • Relative contribution of each substrate to the inflammatory phenotype not dissected

Open questions

Synthesis pass · forward-looking unresolved questions
  • How PIM2 selects among its many substrates in different cellular contexts — whether through scaffolding proteins, subcellular compartmentalization, or differential expression — remains a major unresolved question, as does the structural basis of its constitutive activity and whether its kinase-independent scaffolding functions are broadly relevant.
  • No systematic substrate-selectivity mechanism described
  • No structure with a physiological peptide substrate
  • Kinase-independent functions documented only for TTP and HIF-1α co-activation

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 14
Localization
GO:0005829 cytosol 1
Pathway
R-HSA-1430728 Metabolism 6 R-HSA-162582 Signal Transduction 4 R-HSA-168256 Immune System 4 R-HSA-5357801 Programmed Cell Death 4 R-HSA-1640170 Cell Cycle 3
Partners
4E-BP1BADFOXP3HK2HSF1PKM2TSC2USP27X

Evidence

Reading pass · 39 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 PIM-2 phosphorylates the pro-apoptotic protein BAD on serine 112, inhibiting BAD-induced apoptosis and contributing to pro-survival signaling in hematopoietic cells. In vitro kinase assay, overexpression rescue experiments in FDCP1 cells, Western blot The Journal of biological chemistry High 12954615
2003 PIM-2 maintains rapamycin-resistant phosphorylation of the translational repressor 4E-BP1 and phosphorylates BAD, promoting cell survival and cell size maintenance independently of the PI3K/Akt/TOR pathway. Constitutive expression in hematopoietic cells, rapamycin treatment, phosphorylation analysis, cell size and mitochondrial potential assays Genes & development High 12869584
1995 PIM-2 shares substrate preference and non-AUG initiation codon usage with PIM-1, and is X-linked; proviral activation of PIM-2 compensates for PIM-1 loss in Eµ-myc lymphomagenesis, establishing functional redundancy. PCR-based gene identification, proviral tagging screen in Eµ-myc/Pim-1−/− compound mutant mice, sequence analysis The EMBO journal High 7781606
2004 PIM-2 promotes cell survival through NF-κB activation by inducing phosphorylation of the serine/threonine 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. Overexpression, dominant-negative constructs, NF-κB reporter assays, Co-IP, in vivo lymphoma model Cancer research High 15548703
2009 Crystal structure of PIM2 kinase solved in complex with an organoruthenium inhibitor, revealing key differences from PIM1 at the ATP-binding site that can be exploited for isoform-selective inhibitor design. X-ray crystallography PloS one High 19841674
2013 PIM2 directly phosphorylates TSC2 on Ser-1798, relieving TSC2-mediated suppression of mTOR-C1, thereby driving myeloma cell proliferation. In vitro kinase assay, shRNA knockdown, selective small-molecule inhibitor, mTOR-C1 activity assays Blood High 23818547
2013 PIM2 directly phosphorylates pyruvate kinase M2 (PKM2) on Thr-454, increasing PKM2 protein levels and promoting the Warburg effect, aerobic glycolysis, and co-activation of HIF-1α and β-catenin in cancer cells. Co-IP, in vitro kinase assay, phosphorylation-defective mutants, metabolic flux assays The Journal of biological chemistry High 24142698
2015 PIM-2 kinase phosphorylates the N-terminal domain of Foxp3 at several sites, leading to decreased suppressive function of regulatory T cells and altered Treg lineage stability; pharmacological or genetic inhibition of PIM-2 upregulates Treg suppressive function. In vitro kinase assay, Pim-2 genetic knockout in Treg cells, pharmacological inhibition, DSS colitis model The Journal of biological chemistry High 25987564
2018 PIM2 directly binds and phosphorylates hexokinase-II (HK2) on Thr473, promoting HK2 protein stability via the chaperone-mediated autophagy (CMA) pathway, increasing HK2 enzyme activity and glycolysis, and enhancing breast cancer cell growth and paclitaxel resistance. Co-IP, in vitro kinase assay, site-directed mutagenesis, CMA pathway analysis, in vitro and in vivo tumor models Oncogene High 29985480
2019 PIM2 phosphorylates HSF1 at Thr120, disrupting HSF1 binding to the E3 ubiquitin ligase FBXW7 and thereby increasing HSF1 protein stability; phospho-HSF1 Thr120 promotes PD-L1 expression by binding to the PD-L1 promoter. In vitro kinase assay, Co-IP, ubiquitination assay, ChIP, site-directed mutagenesis, in vivo tumor models Cancer research High 31409638
2011 RAG-induced DNA double-strand breaks signal through ATM to induce PIM2 kinase expression in pre-B cells; PIM2 phosphorylates BAD to antagonize BAX pro-apoptotic function, promoting survival but with antiproliferative effects distinct from IL-7-induced PIM1. Genetic models (RAG-deficient, ATM-deficient), retroviral expression, BAD phosphorylation analysis, cell cycle assays The Journal of experimental medicine High 22201128
2019 PIM2 directly phosphorylates AMPKα1 on Thr467, decreasing AMPKα1 kinase activity, which in turn promotes aerobic glycolysis and tumor growth in endometrial cancer. Co-IP, in vitro kinase assay, site-directed mutagenesis, metabolic assays, in vivo tumor models Oncogene High 31358902
2010 PIM-2 phosphorylates the cell cycle inhibitor p21(Cip1/WAF1) on Thr145 both in vitro and in vivo, enhancing p21 protein stability and inducing G1/S cell cycle arrest in HCT116 cells. In vitro kinase assay, overexpression/knockdown, Western blot, cell cycle analysis The international journal of biochemistry & cell biology High 20307683
2017 PIM2 identifies RSK2 (ribosomal protein S6 kinase A3) as a novel substrate/target in FLT3-ITD AML; ectopic RSK2 expression rescues viability of Pim2-depleted AML cells, placing RSK2 downstream of PIM2 in a pro-survival pathway. High-throughput transcriptomic and proteomic analysis of Pim2-depleted cells, ectopic RSK2 rescue, in vivo xenograft Leukemia Medium 28914261
2021 PIM2 directly phosphorylates PFKFB3 on Ser478, enhancing PFKFB3 protein stability via the ubiquitin-proteasome pathway, promoting glycolysis and paclitaxel resistance in breast cancer. Mass spectrometry, Co-IP, in vitro kinase assay, site-directed mutagenesis, ubiquitination assay, in vivo models Clinical and translational medicine High 33931981
2022 PIM2 phosphorylates PFKFB4 on Thr140, promoting PFKFB4 protein expression via the ubiquitin-proteasome pathway and enhancing glycolysis and cell growth in endometriosis. Co-IP, in vitro kinase assay, site-directed mutagenesis, ubiquitination assay, in vivo models Cell death & disease High 36109523
2020 PIM2 phosphorylates FBP1 on Ser144, abrogating FBP1 interaction with NF-κB p65 and promoting p65 protein stability via CHIP-mediated proteasome pathway, thereby increasing PD-L1 expression. Immunoaffinity purification, Co-IP, in vitro kinase assay, ubiquitination assay, in vivo tumor models, PIM2-KO mice Theranostics High 32754266
2016 PIM2 phosphorylates Bim on Ser65, targeting Bim for proteasomal degradation, thereby protecting H9c2 cardiomyocytes from hypoxia/reoxygenation-induced apoptosis; Co-IP confirmed PIM2-Bim physical interaction. Co-IP, site-directed mutagenesis (Bim S65A), proteasome inhibitor MG132, overexpression/knockdown Environmental toxicology and pharmacology Medium 27770661
2015 PIM2 promotes cell cycle progression in plasmablasts by acting on CDC25A and p27Kip1, and inhibits caspase 3-driven apoptosis through BAD phosphorylation and cytoplasmic stabilization of p21Cip1 during B-cell differentiation into plasma cells. Specific inhibition strategies including morpholino RNA antisense, Western blot, cell cycle and apoptosis assays Blood Medium 35108359
2015 PIM-2 kinase negatively regulates T cell responses to alloantigen in contrast to PIM-1 and PIM-3; PIM-2-deficient T cells show increased Th1 differentiation, proliferation, and migration, resulting in accelerated GVHD, while PIM-2 deficiency enhances CD8+ T cell anti-tumor responses. Genetic knockout, bone marrow transplantation model, adoptive transfer, tumor rejection assays The Journal of clinical investigation High 29781812
2013 PIM-2 is an essential component of the UV damage response: PIM-2 expression and activity increase upon UVC radiation, and PIM-2 promotes DNA lesion removal and cell survival through increased E2F-1 and ATM activity, placing PIM-2 upstream of E2F-1 and ATM. Overexpression/knockdown, UV irradiation, γH2AX quantification, ATM inhibitor epistasis, E2F-1 silencing The Journal of biological chemistry Medium 23760264
2015 CHES1/FOXN3 transcription factor directly binds the PIM2 promoter to repress PIM2 expression; reduced PIM2 in CHES1-expressing cells leads to decreased phosphorylation of the PIM2 target 4E-BP1, and overexpression of PIM2 or eIF4E partially reverses CHES1-mediated antiproliferative effects. ChIP, shRNA knockdown, overexpression rescue, phosphorylation analysis Molecular biology of the cell High 24403608
2015 PIM2 promotes persistent STAT3 activation through induction of cytokines, and STAT3 activation in turn increases PIM2 expression, forming a positive feedback loop that drives EMT and ZEB1-dependent migration and invasion in breast cancer. Knockdown/overexpression, cytokine measurement, signaling pathway analysis Cancer science Medium 25854938
2018 PIM2 physically interacts with tristetraprolin (TTP) and promotes its degradation via the ubiquitin-proteasome pathway independently of PIM2 kinase activity, de-repressing TTP-mediated inhibition of breast cancer cell proliferation and migration. Co-IP, pulldown, ubiquitination assay, kinase-dead mutant analysis, in vivo xenograft Molecular oncology Medium 29570932
2020 PIM2 activates NF-κB signaling in hepatocellular carcinoma by upregulating phosphorylation of RIPK2, and TNFα induces PIM2 expression while PIM2 overexpression upregulates TNFα, creating a positive feedback loop. Knockdown/overexpression, phosphorylation analysis, Western blot, in vivo tumor models Cell death & disease Medium 32641749
2015 PIM2 protein has a cytoplasmic localization in leukemic cells; all three PIM2 isoforms have very short half-lives and are degraded by the proteasome without ubiquitination, as purified 20S proteasome can degrade PIM2 in vitro; PIM2 mRNA is regulated by erythropoietin via STAT5. Subcellular fractionation, proteasome inhibitor assays, E1 inhibitor (Pyr41), in vitro 20S proteasome degradation assay, STAT5 inhibition Bioscience reports Medium 26500282
2014 PIM2 interacts with HIF-1α (particularly its transactivation domain) as a co-factor (not upstream kinase), enhancing HIF-1α transcriptional activity in a positive feedback loop where HIF-1α also induces PIM2 expression via HREs in the PIM2 promoter. Co-IP, HRE reporter assay, ChIP, overexpression/knockdown, metabolic assays PloS one Medium 24505470
2012 PIM-2 activates cell cycle arrest and apoptosis in a kinase-dependent, p73-dependent manner when the 34 kDa HA-tagged isoform is expressed: induces T14/Y15 phosphorylation of CDK2, proteasome-dependent downregulation of CDC25A, and upregulation of p57, E2F-1, and p73. Transient overexpression, kinase-dead mutant, p73 dominant negative, cell cycle analysis, Western blot PloS one Medium 22506047
2007 PIM-2 kinase is required for survival of epiphyseal chondrocytes independently of Akt-1; PIM-2 modulates BAD activity and promotes expression and organization of autophagic proteins LC3 and Beclin-1, as well as lysosomal acidification, inducing autophagy as a cell survival mechanism. SiRNA knockdown, rapamycin treatment, BAD phosphorylation analysis, LC3/Beclin-1 expression, lysosomal assays Journal of cellular physiology Medium 17476689
2008 PIM2 overexpression in liver cells maintains phosphorylation of 4E-BP1 and BAD, promoting cell survival in IL-3-deprived conditions, while PIM2 knockdown abolishes this survival, confirming 4E-BP1 and BAD as PIM2 downstream effectors in hepatocellular carcinoma. Ectopic expression, siRNA knockdown, phosphorylation analysis, IL-3 deprivation assay The Journal of surgical research Medium 18675992
2024 PIM2 phosphorylates USP27X, promoting its deubiquitylation activity for MYC protein, thereby increasing MYC stability and HK2-mediated aerobic glycolysis in breast cancer; validated in PIM2-knockout mice. Co-IP, in vitro kinase assay, deubiquitylation assay, MYC stability analysis, PIM2-KO mice Oncogene High 38969771
2025 PIM2 directly phosphorylates multiple glycolytic enzymes during M1 macrophage polarization: PGK1 on Ser203, PDHA1 on Ser300, and PFKFB2 on Ser466, promoting glycolytic reprogramming; conditional knockout of Pim2 in macrophages attenuates M1 polarization and arthritis in CIA model. In vitro kinase assay, site-specific phosphorylation, macrophage-specific conditional KO, CIA model Cellular & molecular immunology High 40000906
2019 In CML stem cells, PIM2 expression is promoted by both a BCR-ABL-dependent STAT5-mediated pathway and a BCR-ABL-independent (imatinib-resistant) STAT4-mediated pathway; PIM2 maintains BAD phosphorylation to confer imatinib resistance. Single-cell RNA-seq, genetic separation of CML stem cells and normal HSCs, BAD phosphorylation analysis, combined PIM inhibitor + imatinib treatment, mouse CML model Proceedings of the National Academy of Sciences of the United States of America High 31068472
2009 PIM2 requires PI3K and Notch1 signaling (acting downstream of TLR2-MyD88) to induce COX-2 and MMP-9 expression in macrophages; Notch1 mediates recruitment of CSL and NF-κB to respective promoters. Pharmacological inhibition, dominant-negative Notch1, ChIP, NF-κB nuclear translocation assays PloS one Low 19290049
2022 PIM2 directly interacts with NLRP3 and promotes LPS-triggered NLRP3 inflammasome activation (Caspase-1, IL-1β, NLRP3, ASC) in macrophages; PIM2 knockout alleviates ARDS severity in vivo. Co-IP, overexpression/knockdown, PIM2-KO mice, LPS-ARDS model Biochemical and biophysical research communications Medium 33333710
2017 PIM2 phosphorylates eIF4B in prostate cancer cells; Pim-2 siRNA reduces p-eIF4B and increases apoptosis, while Pim-2 overexpression increases p-eIF4B and decreases apoptosis. XIAP is downstream of the Pim-2/eIF4B pathway. Transfection/siRNA, Western blot for p-eIF4B, apoptosis analysis, immunofluorescence co-localization Pathology oncology research Medium 29124675
2019 TRAF3 deficiency in B cells leads to induction of PIM2 through a STAT3-dependent (not NF-κB2-dependent) mechanism; elevated PIM2 in TRAF3-deficient cells increases c-Myc protein levels with reduced c-Myc ubiquitination, in a PIM2-dependent manner. Genetic knockout, STAT3 inhibition, PIM inhibitor treatment, ubiquitination analysis Scientific reports Medium 31501481
2025 PIM2 inhibition reduces phosphorylated BAD production and activates ISR (integrated stress response)-mediated NOXA expression, shifting plasma cells toward MCL1 dependence; combined PIM2/MCL1 inhibition synergistically controls tumor growth in xenograft models. PIM2 inhibition (pharmacological and morpholino antisense), ISR pathway analysis, NOXA expression, xenograft models Nature communications Medium 39747141
2022 PIM2 kinase regulates bone resorptive activity of osteoclasts by controlling expression of the V-ATPase a3 isoform; siRNA knockdown of Pim-2 selectively reduced RANKL-induced resorptive activity without affecting osteoclastogenesis, while Pim-2 overexpression stimulated a3 subunit expression. siRNA knockdown, retroviral overexpression, RANKL-induced osteoclastogenesis, dentin disc bone resorption assay Journal of cellular physiology Medium 35696529

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 280 12869584
2003 The PIM-2 kinase phosphorylates BAD on serine 112 and reverses BAD-induced cell death. The Journal of biological chemistry 235 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 112 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 90 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
2019 Phosphorylation of HSF1 by PIM2 Induces PD-L1 Expression and Promotes Tumor Growth in Breast Cancer. Cancer research 75 31409638
2015 Pim-2 Kinase Influences Regulatory T Cell Function and Stability by Mediating Foxp3 Protein N-terminal Phosphorylation. The Journal of biological chemistry 75 25987564
2009 Crystal structure of the PIM2 kinase in complex with an organoruthenium inhibitor. PloS one 71 19841674
2007 Pim-1 and Pim-2 kinases are required for efficient pre-B-cell transformation by v-Abl oncogene. Blood 65 18042805
2005 Pim-2 upregulation: biological implications associated with disease progression and perinueral invasion in prostate cancer. The Prostate 65 16015593
2014 PIM kinases are essential for chronic lymphocytic leukemia cell survival (PIM2/3) and CXCR4-mediated microenvironmental interactions (PIM1). Molecular cancer therapeutics 58 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 51 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
2011 RAG-induced DNA double-strand breaks signal through Pim2 to promote pre-B cell survival and limit proliferation. The Journal of experimental medicine 42 22201128
2022 Phosphorylation of PFKFB4 by PIM2 promotes anaerobic glycolysis and cell proliferation in endometriosis. Cell death & disease 41 36109523
2015 Persistent activation of STAT3 by PIM2-driven positive feedback loop for epithelial-mesenchymal transition in breast cancer. Cancer science 41 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 39 19821157
2019 Negative regulation of AMPKα1 by PIM2 promotes aerobic glycolysis and tumorigenesis in endometrial cancer. Oncogene 37 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 35 28008178
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 34 20307683
2018 PIM-2 protein kinase negatively regulates T cell responses in transplantation and tumor immunity. The Journal of clinical investigation 33 29781812
2016 The role of PIM1/PIM2 kinases in tumors of the male reproductive system. Scientific reports 33 27901106
2014 CHES1/FOXN3 regulates cell proliferation by repressing PIM2 and protein biosynthesis. Molecular biology of the cell 33 24403608
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
2021 Protein kinase PIM2: A simple PIM family kinase with complex functions in cancer metabolism and therapeutics. Journal of Cancer 32 33854618
2007 PIM-2 is an independent regulator of chondrocyte survival and autophagy in the epiphyseal growth plate. Journal of cellular physiology 32 17476689
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
2020 PIM2 promotes hepatocellular carcinoma tumorigenesis and progression through activating NF-κB signaling pathway. Cell death & disease 28 32641749
2007 Pim2 complements Flt3 wild-type receptor in hematopoietic progenitor cell transformation. Leukemia 28 17943165
2025 Targeting macrophage polarization by inhibiting Pim2 alleviates inflammatory arthritis via metabolic reprogramming. Cellular & molecular immunology 27 40000906
2017 RSK2 is a new Pim2 target with pro-survival functions in FLT3-ITD-positive acute myeloid leukemia. Leukemia 27 28914261
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
2014 PIM2 kinase is induced by cisplatin in ovarian cancer cells and limits drug efficacy. Journal of proteome research 24 25099161
2018 MicroRNA-26b-5p enhances T cell responses by targeting PIM-2 in hepatocellular carcinoma. Cellular signalling 23 30593845
2017 Inflammation and stem markers association to PIM1/PIM2 kinase-induced tumors in breast and uterus. Oncotarget 23 28938604
2015 Control of Pim2 kinase stability and expression in transformed human haematopoietic cells. Bioscience reports 23 26500282
2013 The over-expression of Pim-2 promote the tumorigenesis of prostatic carcinoma through phosphorylating eIF4B. The Prostate 22 23813671
2022 PIM2 Expression Induced by Proinflammatory Macrophages Suppresses Immunotherapy Efficacy in Hepatocellular Carcinoma. Cancer research 21 35802648
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
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
2023 PIM2 Promotes the Development of Ovarian Endometriosis by Enhancing Glycolysis and Fibrosis. Reproductive sciences (Thousand Oaks, Calif.) 16 37059967
2019 TRAF3 regulates the oncogenic proteins Pim2 and c-Myc to restrain survival in normal and malignant B cells. Scientific reports 16 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
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
2021 Myeloma-Bone Interaction: A Vicious Cycle via TAK1-PIM2 Signaling. Cancers 9 34503251
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
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
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 PIM2 inhibition promotes MCL1 dependency in plasma cells involving integrated stress response-driven NOXA expression. Nature communications 3 39747141
2024 Regnase-1 D141N mutation induces CD4+ T cell-mediated lung granuloma formation via upregulation of Pim2. International immunology 3 38700370
2023 Final step of B-cell differentiation into plasmablasts; the right time to activate plasma cell PIM2 kinase. Immunology letters 3 37207916
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 2 40865347
2023 Protective effects of cell permeable Tat-PIM2 protein on oxidative stress induced dopaminergic neuronal cell death. Heliyon 2 37223703
2022 Pim-2 regulates bone resorptive activity of osteoclasts via V-ATPase a3 isoform expression in periodontal disease. Journal of cellular physiology 2 35696529
2025 Modified Xi-Jiao-Di-Huang Decoction Alleviates Sepsis via Regulating Macrophage Polarization by Inhibiting the PIM2/NF-κB Pathway. Journal of inflammation research 1 40248592
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