Table 1 Pim Kinase phosphorylation substrates
From: Targeting Pim kinases in hematological cancers: molecular and clinical review
| Â | Direct Phosphorylation Targets | Effect on Oncogenesis | Pim(s) |
|---|---|---|---|
Transcriptional Activation | p65/RelA [36] | NF-κB signaling pathway | Pim1 |
Cot (MAP3K8/Mitogen-Activated Protein Kinase Kinase Kinase 8) [37] | NF-κB signaling pathway | Pim2 | |
c-MyC (myc Proto-Oncogene Protein) [38] | c-Myc and NF-κB Signaling pathways | Pim-1 and 2 | |
H3 (Histone H3) [39] | Enhance c-Myc transcriptional Activity | Pim-1 | |
C-MyB and A-Myb (Myb Proto-Oncogene) [40] | Enhance transcriptional activities; Feedback: c-Myb can regulate c-Myc [41] | Pim-1 | |
p100 (Nuclear Factor Kappa B Subunit 2) [42] | Up-regulates c-Myb; NF-κB signaling pathway | Pim-1 | |
Runx1 and Runx2 (Acute Myeloid Leukemia Gene 1 and 2) [43] | (CBF) family of transcription factors; Required for Myc and Myb activity in leukemia [44] | Pim-1 | |
Notch1 and Notch3 (Notch receptor 1 and 3) [45] | Transcriptional Activators (cleaved); activate c-Myc | Pim-1, −2, −3 | |
Proliferation and Cell Cycle | p21CIP1/WAF1 (CDKN1A/cyclin Dependent Kinase Inhibitor 1A) [46, 47] | Cell Cycle Progression | Pim-1 and 2 |
p27KIP1 (CDKN1B/cyclin Dependent Kinase Inhibitor 1B) [48] | Cell Cycle Progression | Pim-1, −2, −3 | |
Cell Cycle Progression | Pim-1 | ||
C-TAK1 (protein kinase Cdc25 C-associated kinase 1) [49] | Cell Cycle Regulator | Pim-1 | |
Cell Cycle Progression | Pim-1 | ||
NuMA (Nuclear Mitotic Apparatus) [52] | Mitosis | Pim-1 | |
HP1γ (heterochromatin-associated protein 1 gamma) [53] | Mitosis | Pim-1 | |
Translation and Cell Metabolism | TSC2 (TSC Complex Subunit 2) [54] | Enhanced Protein Translation | Pim-2 |
4E-BP1 (Eukaryotic Translation Initiation Factor 4E Binding Protein 1) [55] | Enhanced Protein Translation; TSC2 target gene | Pim-2 | |
PRAS40 (AKT1 Substrate 1) [56] | Increased mTOR activation of 4E-BP1 and p70S6K | Pim-1 | |
eIF4B (Eukaryotic Translation Initiation Factor 4B) [57] | Translation Initiation | Pim-1 | |
LKB1 (Serine/Threonine Kinase 11) [58] | Cell Metabolism and Energy Production | Pim-1 | |
Apoptosis and Cellular Invasion | Bad (BCL2 Associated Agonist of Cell Death) [59] | Anti-apoptotic release of Bcl-XL | Pim-1, −2, −3 |
Bim (BCL2 Like 11) [60] | Anti-apoptotic | Pim-2 | |
ASK1 (Apoptosis signaling kinase 1) [61] | Anti-Apoptotic to stress and inflammation | Pim-1 | |
p53 degradation and transactivation | Pim-1 and 2 | ||
AR (androgen receptor) [64] | Pim-1 | ||
14–3-3ζ [65] | AR co-activator | Pim-1 | |
NKX3.1 (NK3 Homeobox 1) [66] | 14–3-3ζ functional partner | Pim-1 | |
Lymphoid Signaling | NFATC1 (Nuclear Factor of Activated T Cells 1) [67] | T-cell signaling, bone formation, immunotherapy | Pim-1, −2, −3 |
T-cell Regulation; JAK/STAT Signaling | Pim-1 | ||
FLT3 (Fms Related Receptor Tyrosine Kinase 3) [70] | STAT5a/b regulation and cytokine-sensitive signaling pathways | Pim-1 | |
Cell trafficking through ligands, such as CXCL12 (C-X-C Motif Chemokine Ligand 12) | Pim-1 and − 3 | ||
H19 [73] | lncRNA involved in stem cell signature | Pim-1 | |
ABCB1 and ABCG2 (BCRP) ATP Binding Cassette Subfamily G Member [31, 33] | Drug efflux; involved in drug resistance | Pim-1 |