Gene Symbol: Pip5k1a
Description: phosphatidylinositol-4-phosphate 5-kinase, type 1 alpha
Alias: PI4P5K-I[a], PIP5K1-alpha, PIP5KIalpha, Pipk5a, phosphatidylinositol 4-phosphate 5-kinase type-1 alpha, 68 kDa type I phosphatidylinositol 4-phosphate 5-kinase, phosphatidylinositol 4-phosphate 5-kinase type I alpha, ptdIns(4)P-5-kinase 1 alpha
Species: mouse
Products:     Pip5k1a

Top Publications

  1. Chang J, Field S, Rameh L, Carpenter C, Cantley L. Identification and characterization of a phosphoinositide phosphate kinase homolog. J Biol Chem. 2004;279:11672-9 pubmed
    ..These results suggest that PIPKH acts as a scaffold to localize and regulate type I PI(4)P 5-kinases and the synthesis of PI(3,4,5)P(3). ..
  2. Wang Y, Chen X, Lian L, Tang T, Stalker T, Sasaki T, et al. Loss of PIP5KIbeta demonstrates that PIP5KI isoform-specific PIP2 synthesis is required for IP3 formation. Proc Natl Acad Sci U S A. 2008;105:14064-9 pubmed publisher
    ..PIP5KIbeta-null mice had normal platelet counts. In contrast to platelets lacking PIP5KIalpha, platelets lacking PIP5KIbeta exhibited impaired aggregation accompanied by disaggregation...
  3. Vallejo Illarramendi A, Zang K, Reichardt L. Focal adhesion kinase is required for neural crest cell morphogenesis during mouse cardiovascular development. J Clin Invest. 2009;119:2218-30 pubmed publisher
    ..Our results indicate that FAK plays an essential role in cardiac outflow tract development by promoting the activation of molecules such as Crkl and Erk1/2...
  4. Volpicelli Daley L, Lucast L, Gong L, Liu L, Sasaki J, Sasaki T, et al. Phosphatidylinositol-4-phosphate 5-kinases and phosphatidylinositol 4,5-bisphosphate synthesis in the brain. J Biol Chem. 2010;285:28708-14 pubmed publisher
  5. Ishihara H, Shibasaki Y, Kizuki N, Wada T, Yazaki Y, Asano T, et al. Type I phosphatidylinositol-4-phosphate 5-kinases. Cloning of the third isoform and deletion/substitution analysis of members of this novel lipid kinase family. J Biol Chem. 1998;273:8741-8 pubmed
    ..Surprisingly, a kinase-deficient substitution mutant also induced an abnormal actin polymerization, suggesting a role of PIP5Ks via structural interactions with other molecules. ..
  6. Zhang J, Luo R, Wu H, Wei S, Han W, Li G. Role of type Ialpha phosphatidylinositol-4-phosphate 5-kinase in insulin secretion, glucose metabolism, and membrane potential in INS-1 beta-cells. Endocrinology. 2009;150:2127-35 pubmed publisher
    ..Taken together, our data suggest that PIP5K-Ialpha may play an important role in both the proximal and distal steps of signaling cascade for insulin secretion in beta-cells. ..
  7. Mao Y, Yamaga M, Zhu X, Wei Y, Sun H, Wang J, et al. Essential and unique roles of PIP5K-gamma and -alpha in Fcgamma receptor-mediated phagocytosis. J Cell Biol. 2009;184:281-96 pubmed publisher
  8. Weixel K, Edinger R, Kester L, Guerriero C, Wang H, Fang L, et al. Phosphatidylinositol 4-phosphate 5-kinase reduces cell surface expression of the epithelial sodium channel (ENaC) in cultured collecting duct cells. J Biol Chem. 2007;282:36534-42 pubmed
    ..We conclude that membrane turnover events regulating ENaC surface expression and activity in oocytes and CCD cells can be regulated by PI5KIalpha. ..
  9. Kisseleva M, Feng Y, Ward M, Song C, Anderson R, Longmore G. The LIM protein Ajuba regulates phosphatidylinositol 4,5-bisphosphate levels in migrating cells through an interaction with and activation of PIPKI alpha. Mol Cell Biol. 2005;25:3956-66 pubmed
    ..Thus, in addition to its effects upon Rac activity Ajuba can also influence cell migration through regulation of PI(4,5)P2 synthesis through direct activation of PIPKIalpha enzyme activity. ..

More Information


  1. Davis J, Rock C, Cheng M, Watson J, Ashmun R, Kirk H, et al. Complementation of growth factor receptor-dependent mitogenic signaling by a truncated type I phosphatidylinositol 4-phosphate 5-kinase. Mol Cell Biol. 1997;17:7398-406 pubmed
    ..These results suggest a role for PIP5K-Ibeta in receptor endocytosis and that the truncated enzyme compensated for a mitogenically defective CSF-1R by interfering with this process. ..
  2. Ishihara H, Shibasaki Y, Kizuki N, Katagiri H, Yazaki Y, Asano T, et al. Cloning of cDNAs encoding two isoforms of 68-kDa type I phosphatidylinositol-4-phosphate 5-kinase. J Biol Chem. 1996;271:23611-4 pubmed
    ..Molecular identification of type I PI4P5K isoforms in insulin-secreting cells should provide insights into the role of phosphatidylinositol metabolism in regulated exocytosis of insulin-containing large dense core vesicles. ..
  3. Wright B, Loo L, Street S, Ma A, Taylor Blake B, Stashko M, et al. The lipid kinase PIP5K1C regulates pain signaling and sensitization. Neuron. 2014;82:836-47 pubmed publisher
    ..Our studies reveal that PIP5K1C regulates PIP2-dependent nociceptive signaling and suggest that PIP5K1C is a therapeutic target for chronic pain. ..
  4. Wang L, Li G, Sugita S. A central kinase domain of type I phosphatidylinositol phosphate kinases is sufficient to prime exocytosis: isoform specificity and its underlying mechanism. J Biol Chem. 2005;280:16522-7 pubmed
  5. Legate K, Montag D, Böttcher R, Takahashi S, Fassler R. Comparative phenotypic analysis of the two major splice isoforms of phosphatidylinositol phosphate kinase type I? in vivo. J Cell Sci. 2012;125:5636-46 pubmed publisher
  6. Pajukanta P, Bodnar J, Sallinen R, Chu M, Airaksinen T, Xiao Q, et al. Fine mapping of Hyplip1 and the human homolog, a potential locus for FCHL. Mamm Genome. 2001;12:238-45 pubmed
    ..Further studies identifying and sequencing the Hyplip1 gene will show whether the same gene predisposes to hyperlipidemia in human and mouse. ..
  7. Jones D, Morris J, Morgan C, Kondo H, Irvine R, Cockcroft S. Type I phosphatidylinositol 4-phosphate 5-kinase directly interacts with ADP-ribosylation factor 1 and is responsible for phosphatidylinositol 4,5-bisphosphate synthesis in the golgi compartment. J Biol Chem. 2000;275:13962-6 pubmed
    ..ARF1 increased Type I PIP 5-kinase activity in a guanine nucleotide-dependent manner, identifying this enzyme as a direct effector for ARF1. ..
  8. Anderson R, Boronenkov I, Doughman S, Kunz J, Loijens J. Phosphatidylinositol phosphate kinases, a multifaceted family of signaling enzymes. J Biol Chem. 1999;274:9907-10 pubmed
  9. Zhu T, Chappel J, Hsu F, Turk J, Aurora R, Hyrc K, et al. Type I phosphotidylinosotol 4-phosphate 5-kinase ? regulates osteoclasts in a bifunctional manner. J Biol Chem. 2013;288:5268-77 pubmed publisher
    ..The combined arrested differentiation and disorganized cytoskeleton of PIP5KI?-transduced osteoclasts compromises bone resorption. Thus, optimal PIP5KI? and PI(4,5)P(2) expression, by osteoclasts, are essential for skeletal homeostasis. ..
  10. Wang Y, Litvinov R, Chen X, Bach T, Lian L, Petrich B, et al. Loss of PIP5KIgamma, unlike other PIP5KI isoforms, impairs the integrity of the membrane cytoskeleton in murine megakaryocytes. J Clin Invest. 2008;118:812-9 pubmed publisher
    ..These observations further demonstrate that individual PIP5KI isoforms fulfill distinct functions within cells. ..
  11. Tolias K, Hartwig J, Ishihara H, Shibasaki Y, Cantley L, Carpenter C. Type Ialpha phosphatidylinositol-4-phosphate 5-kinase mediates Rac-dependent actin assembly. Curr Biol. 2000;10:153-6 pubmed
    ..These results demonstrate that PIP 5-kinase alpha is a critical mediator of thrombin- and Rac-dependent actin assembly. ..
  12. Divecha N, Roefs M, Halstead J, D Andrea S, Fernandez Borga M, Oomen L, et al. Interaction of the type Ialpha PIPkinase with phospholipase D: a role for the local generation of phosphatidylinositol 4, 5-bisphosphate in the regulation of PLD2 activity. EMBO J. 2000;19:5440-9 pubmed
    ..We show that the physiological requirement of PLD enzymes for PtdIns(4,5)P(2) is critical and that PLD2 activity can be regulated solely by the levels of this key intracellular lipid. ..
  13. Huang P, Yeku O, Zong H, Tsang P, Su W, Yu X, et al. Phosphatidylinositol-4-phosphate-5-kinase alpha deficiency alters dynamics of glucose-stimulated insulin release to improve glucohomeostasis and decrease obesity in mice. Diabetes. 2011;60:454-63 pubmed publisher
    ..The increased first-phase glucose-stimulated release of insulin observed on the normal diet may underlie the partial protection against the elevated serum glucose and obesity seen in type 2 diabetes-like model systems. ..
  14. Hasegawa H, Noguchi J, Yamashita M, Okada R, Sugimoto R, Furuya M, et al. Phosphatidylinositol 4-phosphate 5-kinase is indispensable for mouse spermatogenesis. Biol Reprod. 2012;86:136, 1-12 pubmed publisher
    ..Three PIP5K isozymes, PIP5K1A, PIP5K1B, and PIP5K1C, have been identified in mammals so far...
  15. Kanzaki M, Furukawa M, Raab W, Pessin J. Phosphatidylinositol 4,5-bisphosphate regulates adipocyte actin dynamics and GLUT4 vesicle recycling. J Biol Chem. 2004;279:30622-33 pubmed
    ..In adipocytes, altered PI(4,5)P2 metabolism has marked effects on GLUT4 endocytosis and intracellular vesicle trafficking due to the derangement of actin dynamics. ..
  16. Weernink P, Meletiadis K, Hommeltenberg S, Hinz M, Ishihara H, Schmidt M, et al. Activation of type I phosphatidylinositol 4-phosphate 5-kinase isoforms by the Rho GTPases, RhoA, Rac1, and Cdc42. J Biol Chem. 2004;279:7840-9 pubmed
  17. Akiba Y, Suzuki R, Saito Saino S, Owada Y, Sakagami H, Watanabe M, et al. Localization of mRNAs for phosphatidylinositol phosphate kinases in the mouse brain during development. Brain Res Gene Expr Patterns. 2002;1:123-33 pubmed
    ..The distinct expression for the gene encoding PIPK IIalpha was detected in the postnatal white matter such as the cerebellar medulla, the corpus callosum, the hippocampal fimbriae, and the internal capsule. ..
  18. Szalinski C, Guerriero C, Ruiz W, Docter B, Rbaibi Y, PASTOR SOLER N, et al. PIP5KI? selectively modulates apical endocytosis in polarized renal epithelial cells. PLoS ONE. 2013;8:e53790 pubmed publisher
    ..PtdIns(4,5)P(2) may be required to overcome specific structural constraints that limit the efficiency of apical endocytosis. ..
  19. Galiano F, Ulug E, Davis J. Overexpression of murine phosphatidylinositol 4-phosphate 5-kinase type Ibeta disrupts a phosphatidylinositol 4,5 bisphosphate regulated endosomal pathway. J Cell Biochem. 2002;85:131-45 pubmed
    ..In addition to regulating early steps in endocytosis, these results suggest that mPIP5K-Ibeta acts through PI(4,5)P2 to regulate endosomal trafficking and/or fusion. ..
  20. Halstead J, Savaskan N, van den Bout I, van Horck F, Hajdo Milasinovic A, Snell M, et al. Rac controls PIP5K localisation and PtdIns(4,5)P? synthesis, which modulates vinculin localisation and neurite dynamics. J Cell Sci. 2010;123:3535-46 pubmed publisher
    ..Our findings support a role for PtdIns(4,5)P? synthesis in the regulation of vinculin localisation at focal complexes and ultimately in the regulation of neurite dynamics. ..
  21. Ferrero G, Renner M, Gil G, RodrĂ­guez Berdini L, Caputto B. c-Fos-activated synthesis of nuclear phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P?] promotes global transcriptional changes. Biochem J. 2014;461:521-30 pubmed publisher
    ..We propose c-Fos as a key regulator of nuclear PtdIns(4,5)P? synthesis in response to growth signals that results in c-Fos-dependent transcriptional changes promoted by the newly synthesized lipids. ..