Genomes and Genes
Gene Symbol: PIP5K1C
Description: phosphatidylinositol-4-phosphate 5-kinase type 1 gamma
Alias: LCCS3, PIP5K-GAMMA, PIP5K1-gamma, PIP5Kgamma, phosphatidylinositol 4-phosphate 5-kinase type-1 gamma, diphosphoinositide kinase, phosphatidylinositol-4-phosphate 5-kinase, type I, gamma, ptdIns(4)P-5-kinase 1 gamma, type I PIP kinase
- Ling K, Bairstow S, Carbonara C, Turbin D, Huntsman D, Anderson R. Type I gamma phosphatidylinositol phosphate kinase modulates adherens junction and E-cadherin trafficking via a direct interaction with mu 1B adaptin. J Cell Biol. 2007;176:343-53 pubmed
- Ling K, Doughman R, Firestone A, Bunce M, Anderson R. Type I gamma phosphatidylinositol phosphate kinase targets and regulates focal adhesions. Nature. 2002;420:89-93 pubmed..This defines a mechanism for spatial generation of PtdIns(4,5)P(2) at focal adhesions. ..
- 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..Here, we report the cloning of the third member (PIP5Kgamma) and the characterization of members of the type I PIP5K family...
- van den Bout I, Divecha N. PIP5K-driven PtdIns(4,5)P2 synthesis: regulation and cellular functions. J Cell Sci. 2009;122:3837-50 pubmed publisher..In this Commentary, we review how PIP5Ks are modulated to achieve regulated PtdIns(4,5)P(2) production, and discuss the role of these proteins in different cellular processes. ..
- Bairstow S, Ling K, Su X, Firestone A, Carbonara C, Anderson R. Type Igamma661 phosphatidylinositol phosphate kinase directly interacts with AP2 and regulates endocytosis. J Biol Chem. 2006;281:20632-42 pubmed..Collectively, this evidence implies an important role for PIPKIgamma661 in the AP2-mediated endocytosis of transferrin. ..
- Uličná L, Rohozkova J, Hozak P. Multiple Aspects of PIP2 Involvement in C. elegans Gametogenesis. Int J Mol Sci. 2018;19: pubmed publisher..elegans hermaphrodite. The depletion of PIP2 by type I PIP kinase (PPK-1) kinase RNA interference results in an altered chromosome structure and leads to various defects ..
- Waugh M. Chromosomal Instability and Phosphoinositide Pathway Gene Signatures in Glioblastoma Multiforme. Mol Neurobiol. 2016;53:621-630 pubmed publisher..phosphoinositide phosphatase genes OCRL, MTM1 and MTMR8; copy number amplifications for the chromosome 19 genes PIP5K1C, AKT2 and PIK3R2, and also for the phospholipase C genes PLCB1, PLCB4 and PLCG1 on chromosome 20...
- Wright B, Simpson C, Stashko M, Kireev D, Hull Ryde E, Zylka M, et al. Development of a High-Throughput Screening Assay to Identify Inhibitors of the Lipid Kinase PIP5K1C. J Biomol Screen. 2015;20:655-62 pubmed publisher..Here, we report a novel, high-throughput, microfluidic mobility shift assay to identify inhibitors of PIP5K1C. This assay uses fluorescently labeled phosphatidylinositol 4-phosphate as the substrate and recombinant human ..
- PÅ‚Ã³ciennikowska A, Zdioruk M, Traczyk G, ÅšwiÄ…tkowska A, Kwiatkowska K. LPS-induced clustering of CD14 triggers generation of PI(4,5)P2. J Cell Sci. 2015;128:4096-111 pubmed publisher..and type-I phosphatidylinositol 4-phosphate 5-kinase (PIP5K) isoforms IÎ± and IÎ³ (encoded by Pip5k1a and Pip5k1c, respectively) in the CD14 region...
- Tan X, Sun Y, Thapa N, Liao Y, Hedman A, Anderson R. LAPTM4B is a PtdIns(4,5)P2 effector that regulates EGFR signaling, lysosomal sorting, and degradation. EMBO J. 2015;34:475-90 pubmed publisher..These results reveal an essential layer of EGFR trafficking regulated by LAPTM4B, PtdIns(4,5)P2 signaling, and the ESCRT complex and define a mechanism by which the oncoprotein LAPTM4B can transform cells and promote tumor progression. ..
- Narkis G, Ofir R, Landau D, Manor E, Volokita M, Hershkowitz R, et al. Lethal contractural syndrome type 3 (LCCS3) is caused by a mutation in PIP5K1C, which encodes PIPKI gamma of the phophatidylinsitol pathway. Am J Hum Genet. 2007;81:530-9 pubmed..Of these genes, 30 candidates were sequenced, which identified a single homozygous mutation in PIP5K1C. PIP5K1C encodes phosphatidylinositol-4-phosphate 5-kinase, type I, gamma (PIPKI gamma ), an enzyme that ..
- Auvinen E, Kivi N, Vaheri A. Regulation of ezrin localization by Rac1 and PIPK in human epithelial cells. Exp Cell Res. 2007;313:824-33 pubmed..This localization required the activity of Rac1 and phosphatidylinositol-4-phosphate 5-kinase and involved RhoA. We suggest that localization of ezrin in adherens junctions is regulated by Rac in a manner involving PIPK. ..
- Durand N, Bastea L, Long J, DÃ¶ppler H, Ling K, Storz P. Protein Kinase D1 regulates focal adhesion dynamics and cell adhesion through Phosphatidylinositol-4-phosphate 5-kinase type-l Î³. Sci Rep. 2016;6:35963 pubmed publisher..Our data reveal a novel function for PKD1 as a regulator of FA dynamics and by identifying PIP5KlÎ³ as a novel PKD1 substrate provide mechanistic insight into this process. ..
- Xiong X, Xu Q, Huang Y, Singh R, Anderson R, Leof E, et al. An association between type I? PI4P 5-kinase and Exo70 directs E-cadherin clustering and epithelial polarization. Mol Biol Cell. 2012;23:87-98 pubmed publisher..This could be an important mechanism that regulates E-cadherin clustering and AJ maturation, which is essential for the establishment of solid, polarized epithelial structures. ..
- Le O, Cho O, Tran M, Kim J, Chang S, Jou I, et al. Phosphorylation of phosphatidylinositol 4-phosphate 5-kinase Î³ by Akt regulates its interaction with talin and focal adhesion dynamics. Biochim Biophys Acta. 2015;1853:2432-43 pubmed publisher..Taken together, our results suggested that Akt-mediated PIP5KÎ³90 S555 phosphorylation is a novel regulatory point for talin binding to control PIP2 level at the FAs, thereby modulating FA dynamics and cell motility. ..
- 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). ..
- Krauss M, Haucke V. Functional assay of effectors of ADP ribosylation factor 6 during clathrin/AP-2 coat recruitment to membranes. Methods Enzymol. 2005;404:388-98 pubmed..These methods shall help to mechanistically dissect the role of Arf6 in regulating exo-endocytic vesicle cycling at synapses and in related membrane trafficking events. ..
- Geng F, Zhu W, Anderson R, Leber B, Andrews D. Multiple post-translational modifications regulate E-cadherin transport during apoptosis. J Cell Sci. 2012;125:2615-25 pubmed publisher..The modifications of E-cadherin by O-GlcNAcylation and lack of pro-region processing represent novel mechanisms for rapid regulation of cell surface transport of E-cadherin in response to intoxication. ..
- Akieda Asai S, Zaima N, Ikegami K, Kahyo T, Yao I, Hatanaka T, et al. SIRT1 Regulates Thyroid-Stimulating Hormone Release by Enhancing PIP5Kgamma Activity through Deacetylation of Specific Lysine Residues in Mammals. PLoS ONE. 2010;5:e11755 pubmed publisher..SIRT1 deacetylated two specific lysine residues (K265/K268) in PIP5Kgamma and enhanced PIP5Kgamma enzyme activity. SIRT1-mediated TSH secretion was abolished by PIP5Kgamma knockdown...
- Kahlfeldt N, Vahedi Faridi A, Koo S, Schäfer J, Krainer G, Keller S, et al. Molecular basis for association of PIPKI gamma-p90 with clathrin adaptor AP-2. J Biol Chem. 2010;285:2734-49 pubmed publisher..We postulate a model according to which multiple interactions between PIPKI gamma-p90 and AP-2 lead to spatiotemporally controlled PI(4,5)P(2) synthesis during clathrin-mediated SV endocytosis. ..
- Jafari N, Zheng Q, Li L, Li W, Qi L, Xiao J, et al. p70S6K1 (S6K1)-mediated Phosphorylation Regulates Phosphatidylinositol 4-Phosphate 5-Kinase Type I ? Degradation and Cell Invasion. J Biol Chem. 2016;291:25729-25741 pubmed..These data suggest that S6K1-mediated PIPKI?90 phosphorylation regulates cell migration and invasion by controlling PIPKI?90 degradation. ..
- Xue J, Chen C, Qi M, Huang Y, Wang L, Gao Y, et al. Type I? phosphatidylinositol phosphate kinase regulates PD-L1 expression by activating NF-?B. Oncotarget. 2017;8:42414-42427 pubmed publisher..These results demonstrate that PIPKI?-dependent expression of PD-L1 is likely important for the progression of triple negative breast cancer. ..
- Micucci F, Capuano C, Marchetti E, Piccoli M, Frati L, Santoni A, et al. PI5KI-dependent signals are critical regulators of the cytolytic secretory pathway. Blood. 2008;111:4165-72 pubmed..Our findings delineate a novel mechanism implicating PI5KIalpha and PI5KIgamma isoforms in the synthesis of PIP2 pools critically required for IP3-dependent Ca(2+) response and lytic granule release. ..
- Niiro H, Clark E. Branches of the B cell antigen receptor pathway are directed by protein conduits Bam32 and Carma1. Immunity. 2003;19:637-40 pubmed..Recent studies of Bam32-/- and Carma1-/- mice suggest that each adaptor controls a distinct conduit regulating either only proliferation (Bam32) or both the proliferation and survival of B cells (Carma1). ..
- Thapa N, Choi S, Hedman A, Tan X, Anderson R. Phosphatidylinositol phosphate 5-kinase I?i2 in association with Src controls anchorage-independent growth of tumor cells. J Biol Chem. 2013;288:34707-18 pubmed publisher..This study uncovers a novel mechanism where a phosphoinositide-synthesizing enzyme, PIPKI?i2, functions with the proto-oncogene Src, to regulate oncogenic signaling. ..
- Xu Q, Zhang Y, Wei Q, Huang Y, Hu J, Ling K. Phosphatidylinositol phosphate kinase PIPKIγ and phosphatase INPP5E coordinate initiation of ciliogenesis. Nat Commun. 2016;7:10777 pubmed publisher..Our results reveal that PtdIns(4)P homoeostasis, coordinated by PIPKIγ and INPP5E at the centrosome/ciliary base, is vital for ciliogenesis by regulating the CEP164-dependent recruitment of TTBK2. ..
- Schramp M, Thapa N, Heck J, Anderson R. PIPKI? regulates ?-catenin transcriptional activity downstream of growth factor receptor signaling. Cancer Res. 2011;71:1282-91 pubmed publisher..These results reveal a novel mechanism in which PIPKI? expression and catalytic activity enhance ?-catenin nuclear translocation and expression of its target genes to promote tumorigenic phenotypes. ..
- Li X, Zhou Q, Sunkara M, Kutys M, Wu Z, Rychahou P, et al. Ubiquitylation of phosphatidylinositol 4-phosphate 5-kinase type I ? by HECTD1 regulates focal adhesion dynamics and cell migration. J Cell Sci. 2013;126:2617-28 pubmed publisher..Thus, cycling PIPKI?90 ubiquitylation by HECTD1 and consequent degradation remove PIPKI?90 from talin after on-site PIP2 production, providing an essential regulatory mechanism for FA dynamics and cell migration. ..
- Sun Y, Hedman A, Tan X, Schill N, Anderson R. Endosomal type I? PIP 5-kinase controls EGF receptor lysosomal sorting. Dev Cell. 2013;25:144-55 pubmed publisher..These findings reveal that PIPKI?i5 and SNX5 form a signaling nexus that controls EGFR endosomal sorting, degradation, and signaling. ..
- Xu Q, Zhang Y, Xiong X, Huang Y, Salisbury J, Hu J, et al. PIPKI? targets to the centrosome and restrains centriole duplication. J Cell Sci. 2014;127:1293-305 pubmed publisher..Here, we report that phosphatidylinositol 4-phosphate 5-kinase type-1 gamma (PIP5K1C, hereafter referred to as PIPKI?) plays an important role in centriole fidelity...
- Thapa N, Choi S, Tan X, Wise T, Anderson R. Phosphatidylinositol Phosphate 5-Kinase IÎ³ and Phosphoinositide 3-Kinase/Akt Signaling Couple to Promote Oncogenic Growth. J Biol Chem. 2015;290:18843-54 pubmed publisher..This pathway may represent a signaling nexus required for the survival and growth of metastasizing and circulating tumor cells in vivo. ..
- Choi S, Thapa N, Hedman A, Li Z, Sacks D, Anderson R. IQGAP1 is a novel phosphatidylinositol 4,5 bisphosphate effector in regulation of directional cell migration. EMBO J. 2013;32:2617-30 pubmed publisher..IQGAP1 mutants that lack PIPKI? or PIP? binding lose the ability to control directional cell migration. Collectively, these data reveal a synergy between PIPKI? and IQGAP1 in the control of cell migration. ..
- Wu Z, Li X, Sunkara M, Spearman H, Morris A, Huang C. PIPKI? regulates focal adhesion dynamics and colon cancer cell invasion. PLoS ONE. 2011;6:e24775 pubmed publisher..Taken together, PIPKI? positively regulates focal adhesion dynamics and cancer invasion, most probably through PIP?-mediated vinculin activation...
- Yu Y, Chou R, Chen L, Shyu W, Hsieh S, Wu C, et al. EZH2 regulates neuronal differentiation of mesenchymal stem cells through PIP5K1C-dependent calcium signaling. J Biol Chem. 2011;286:9657-67 pubmed publisher..EZH2 bound to the promoter region of PIP5K1C to suppress its transcription in proliferating hMSCs...
- Gallicchio M, Bach L. Advanced glycation end products inhibit Na+ K+ ATPase in proximal tubule epithelial cells: role of cytosolic phospholipase A2alpha and phosphatidylinositol 4-phosphate 5-kinase gamma. Biochim Biophys Acta. 2010;1803:919-30 pubmed publisher..Transfection of HK2 cells with PIP5Kgamma siRNA prevented AGE-BSA inhibition of NKA activity...
- Carpenter C. Btk-dependent regulation of phosphoinositide synthesis. Biochem Soc Trans. 2004;32:326-9 pubmed..This complex provides a novel shuttling mechanism that allows Btk to regulate the production of the substrate required by both its upstream activator phosphoinositide 3-kinase and its downstream target phospholipase Cgamma2. ..
- Nader G, Ezratty E, Gundersen G. FAK, talin and PIPKI? regulate endocytosed integrin activation to polarize focal adhesion assembly. Nat Cell Biol. 2016;18:491-503 pubmed publisher..We propose that the conformational memory of endocytosed integrin enhances polarized reassembly of FAs to enable directional cell migration. ..
- Sun M, Cai J, Anderson R, Sun Y. Type I ? Phosphatidylinositol Phosphate 5-Kinase i5 Controls the Ubiquitination and Degradation of the Tumor Suppressor Mitogen-inducible Gene 6. J Biol Chem. 2016;291:21461-21473 pubmed..Thus, loss of NEDD4-1 can rescue Mig6 expression in PIPKI?i5 knockdown cells. In this way, PIPKI?i5, NEDD4-1, and Mig6 form a novel molecular nexus that controls EGFR activation and downstream signaling. ..
- Lokuta M, Senetar M, Bennin D, Nuzzi P, Chan K, Ott V, et al. Type Igamma PIP kinase is a novel uropod component that regulates rear retraction during neutrophil chemotaxis. Mol Biol Cell. 2007;18:5069-80 pubmed..Together, our findings identify a previously unknown function for PIPKIgamma661 as a novel component of the backness signal that regulates rear retraction during chemotaxis. ..
- Barsukov I, Prescot A, Bate N, Patel B, Floyd D, Bhanji N, et al. Phosphatidylinositol phosphate kinase type 1gamma and beta1-integrin cytoplasmic domain bind to the same region in the talin FERM domain. J Biol Chem. 2003;278:31202-9 pubmed..The results suggest that ternary complex formation with a single talin FERM domain is unlikely, although both integrins and PIP kinase may bind simultaneously to the talin anti-parallel dimer. ..