Table 2. In vivo targeting of PI5P4Ks.
Genetic Mouse Models | Implicated Isoform | Phenotype |
---|---|---|
Pip4k2a −/− | PI5P4Kα | Normal health and life span [15] |
Pip4k2b −/− | PI5P4Kβ | Normal life span; retarded growth; Insulin sensitivity [16] |
Pip4k2c −/− | PI5P4Kγ | Hyperinflammation; increased helper T cells and reduced regulatory T cells [17] |
Pip4k2a−/− Pip4k2b−/− | PI5P4Kα, PI5P4Kβ | Perinatal lethal [15] |
Pip4k2b−/− Trp53−/− | PI5P4Kβ | Embryonic lethal [15] |
Pip4k2a−/− Pip4k2b+/− Trp53−/− | PI5P4Kα, PI5P4Kβ | Increased tumor free survival compared to Trp53−/− [15] |
KrasLSL-G12D/+ Trp53flx/flx Pip4k2aflx/flx Pip4k2b−/− | PI5P4Kα, PI5P4Kβ | Restricted tumor formation and increased survival compared to KrasLSL-Gi2D/+ Trp53flx/flx [37] |
Tumor Implantation Models | Implicated Isoform | Phenotype |
Xenograft | ||
BT474 Breast cancer p53 mutant cell line | PI5P4Kα, PI5P4Kβ | Impaired tumor growth with kinase knockdown [15] |
THP1 AML cell line | PI5P4Kα | No evidence of leukemic engraftment with kinase knockdown [47] |
SV40 transformed MEF | PI5P4Kβ | Decreased tumor growth with GTP insensitive Pip4k2b [61] |
LN428 GBM cell line | PI5P4Kα | Increased tumor growth with kinase knockdown [53] |
Orthotopic | ||
GBM cell line | PI5P4Kα | Decreased tumor growth with kinase overexpression [53] |
KPS-142 Sarcoma cell line | PI5P4Kα, PI5P4Kβ | Decreased tumor growth with kinase knockdown [37] |