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. Author manuscript; available in PMC: 2022 May 31.
Published in final edited form as: FEBS Lett. 2021 Dec 7;596(1):3–16. doi: 10.1002/1873-3468.14237

Table 2. In vivo targeting of PI5P4Ks.

Summary of the in vivo evidence of targeting PI5P4Ks in mouse models. The top half of the table comprises the phenotypes of the genetic models of kinase deletion, including germline deletions and the GEM model of sarcoma. The bottom half includes the outcomes of the multiple tumor implantation models in which PI5P4Ks were manipulated.

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]