Hyperosmotic stress or receptor activation can promote its translocation from the cytoplasm to the plasma membrane [2,4].

PPIP5K1 overexpression decreases cell sensitivity to cytotoxic agents like etoposide, cisplatin, and sulindac, and reduces p53 phosphorylation on key residues. This protection depends on its catalytic activity. Knockdown of PPIP5K1 expression leads to a 40% reduction in Ser473 phosphorylation in insulin-stimulated L6 myoblasts, suggesting its role in regulating PtdIns(3,4,5)P3-based signalling cascades. Also, knockdown of PPIP5K1 decreases the motility of HeLa cells [1,2,3].

In conclusion, PPIP5K1 plays crucial roles in regulating cell death, ligand competition for polyphosphoinositide-binding domains, and cell motility. The findings from overexpression and knockdown experiments help reveal its functions in cellular processes, which may be relevant to understanding disease mechanisms, especially those related to apoptosis-resistance and abnormal cell motility.

References:

1. Machkalyan, Gayane, Hèbert, Terence E, Miller, Gregory J. 2016. PPIP5K1 Suppresses Etoposide-triggered Apoptosis. In Journal of molecular signaling, 11, 4. doi:10.5334/1750-2187-11-4. https://pubmed.ncbi.nlm.nih.gov/31051014/

2. Gokhale, Nikhil A, Zaremba, Angelika, Janoshazi, Agnes K, Weaver, Jeremy D, Shears, Stephen B. . PPIP5K1 modulates ligand competition between diphosphoinositol polyphosphates and PtdIns(3,4,5)P3 for polyphosphoinositide-binding domains. In The Biochemical journal, 453, 413-26. doi:10.1042/BJ20121528. https://pubmed.ncbi.nlm.nih.gov/23682967/

3. Machkalyan, Gayane, Trieu, Phan, Pétrin, Darlaine, Hébert, Terence E, Miller, Gregory J. 2016. PPIP5K1 interacts with the exocyst complex through a C-terminal intrinsically disordered domain and regulates cell motility. In Cellular signalling, 28, 401-411. doi:10.1016/j.cellsig.2016.02.002. https://pubmed.ncbi.nlm.nih.gov/26854614/

4. Gokhale, Nikhil A, Zaremba, Angelika, Shears, Stephen B. . Receptor-dependent compartmentalization of PPIP5K1, a kinase with a cryptic polyphosphoinositide binding domain. In The Biochemical journal, 434, 415-26. doi:10.1042/BJ20101437. https://pubmed.ncbi.nlm.nih.gov/21222653/