Skip to main content
SpringerLink
Log in

PIPKIIα is widely expressed in hematopoietic-derived cells and may play a role in the expression of alpha- and gamma-globins in K562 cells

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Characterized for the first time in erythrocytes, phosphatidylinositol phosphate kinases (PIP kinases) belong to a family of enzymes that generate various lipid messengers and participate in several cellular processes, including gene expression regulation. Recently, the PIPKIIα gene was found to be differentially expressed in reticulocytes from two siblings with hemoglobin H disease, suggesting a possible relationship between PIPKIIα and the production of globins. Here, we investigated PIPKIIα gene and protein expression and protein localization in hematopoietic-derived cells during their differentiation, and the effects of PIPKIIα silencing on K562 cells. PIPKIIα silencing resulted in an increase in α and γ globins and a decrease in the proliferation of K562 cells without affecting cell cycle progression and apoptosis. In conclusion, using a cell line model, we showed that PIPKIIα is widely expressed in hematopoietic-derived cells, is localized in their cytoplasm and nucleus, and is upregulated during erythroid differentiation. We also showed that PIPKIIα silencing can induce α and γ globin expression and decrease cell proliferation in K562 cells.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Doughman RL, Firestone AJ, Anderson RA (2003) Phosphatidylinositol phosphate kinases put PI4,5P(2) in its place. J Membr Biol 194:77–89

    Article  CAS  PubMed  Google Scholar 

  2. Michell RH, Conroy LA, Finney M, French PJ, Bunce CM, Anderson K, Baxter MA, Brown G, Gordon J, Jenkinson EJ et al (1992) Inositol lipids and phosphates in the proliferation and differentiation of lymphocytes and myeloid cells. Ciba Found Symp 164:2–11 discussion 12–16

    CAS  PubMed  Google Scholar 

  3. Anderson RA, Boronenkov IV, Doughman SD, Kunz J, Loijens JC (1999) Phosphatidylinositol phosphate kinases, a multifaceted family of signaling enzymes. J Biol Chem 274:9907–9910

    Article  CAS  PubMed  Google Scholar 

  4. Bunce MW, Boronenkov IV, Anderson RA (2008) Coordinated activation of the nuclear ubiquitin ligase Cul3-SPOP by the generation of phosphatidylinositol 5-phosphate. J Biol Chem 283:8678–8686

    Article  CAS  PubMed  Google Scholar 

  5. Clarke JH, Wang M, Irvine RF (2010) Localization, regulation and function of type II phosphatidylinositol 5-phosphate 4-kinases. Adv Enzyme Regul 50:12–18

    Article  PubMed Central  PubMed  Google Scholar 

  6. Ling LE, Schulz JT, Cantley LC (1989) Characterization and purification of membrane-associated phosphatidylinositol-4-phosphate kinase from human red blood cells. J Biol Chem 264:5080–5088

    CAS  PubMed  Google Scholar 

  7. Hinchliffe KA, Irvine RF, Divecha N (1996) Aggregation-dependent, integrin-mediated increases in cytoskeletally associated PtdInsP2 (4,5) levels in human platelets are controlled by translocation of PtdIns 4-P 5-kinase C to the cytoskeleton. EMBO J 15:6516–6524

    CAS  PubMed Central  PubMed  Google Scholar 

  8. Wenning MR, Mello MP, Andrade TG, Lanaro C, Albuquerque DM, Saad ST, Costa FF, Sonati MF (2009) PIP4KIIA and beta-globin: transcripts differentially expressed in reticulocytes and associated with high levels of Hb H in two siblings with Hb H disease. Eur J Haematol 83:490–493

    Article  CAS  PubMed  Google Scholar 

  9. Heck JN, Mellman DL, Ling K, Sun Y, Wagoner MP, Schill NJ, Anderson RA (2007) A conspicuous connection: structure defines function for the phosphatidylinositol-phosphate kinase family. Crit Rev Biochem Mol Biol 42:15–39

    Article  CAS  PubMed  Google Scholar 

  10. Boronenkov IV, Loijens JC, Umeda M, Anderson RA (1998) Phosphoinositide signaling pathways in nuclei are associated with nuclear speckles containing pre-mRNA processing factors. Mol Biol Cell 9:3547–3560

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  11. York JD, Odom AR, Murphy R, Ives EB, Wente SR (1999) A phospholipase C-dependent inositol polyphosphate kinase pathway required for efficient messenger RNA export. Science 285:96–100

    Article  CAS  PubMed  Google Scholar 

  12. Bazenet CE, Ruano AR, Brockman JL, Anderson RA (1990) The human erythrocyte contains two forms of phosphatidylinositol-4-phosphate 5-kinase which are differentially active toward membranes. J Biol Chem 265:18012–18022

    CAS  PubMed  Google Scholar 

  13. Jenkins GH, Fisette PL, Anderson RA (1994) Type I phosphatidylinositol 4-phosphate 5-kinase isoforms are specifically stimulated by phosphatidic acid. J Biol Chem 269:11547–11554

    CAS  PubMed  Google Scholar 

  14. Boronenkov IV, Anderson RA (1995) The sequence of phosphatidylinositol-4-phosphate 5-kinase defines a novel family of lipid kinases. J Biol Chem 270:2881–2884

    Article  CAS  PubMed  Google Scholar 

  15. Martin TF (2001) PI(4,5)P(2) regulation of surface membrane traffic. Curr Opin Cell Biol 13:493–499

    Article  CAS  PubMed  Google Scholar 

  16. Matsui T, Yonemura S, Tsukita S (1999) Activation of ERM proteins in vivo by Rho involves phosphatidyl-inositol 4-phosphate 5-kinase and not ROCK kinases. Curr Biol 9:1259–1262

    Article  CAS  PubMed  Google Scholar 

  17. Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods 25:402–408

    Article  CAS  PubMed  Google Scholar 

  18. Machado-Neto JA, Favaro P, Lazarini M, Costa FF, Olalla Saad ST, Traina F (2011) Knockdown of insulin receptor substrate 1 reduces proliferation and downregulates Akt/mTOR and MAPK pathways in K562 cells. Biochim Biophys Acta 1813(8):1404–1411

    Article  CAS  PubMed  Google Scholar 

  19. Chang CW, Chou HY, Lin YS, Huang KH, Chang CJ, Hsu TC, Lee SC (2008) Phosphorylation at Ser473 regulates heterochromatin protein 1 binding and corepressor function of TIF1beta/KAP1. BMC Mol Biol 9:61

    Article  PubMed Central  PubMed  Google Scholar 

  20. Di Pietro R, di Giacomo V, Caravatta L, Sancilio S, Rana RA, Cataldi A (2007) Cyclic nucleotide response element binding (CREB) protein activation is involved in K562 erythroleukemia cells differentiation. J Cell Biochem 100:1070–1079

    Article  PubMed  Google Scholar 

  21. Pass MB, Borregaard N, Cowland JB (2007) Derangement of transcription factor profiles during in vitro differentiation of HL60 and NB4 cells. Leuk Res 31:827–837

    Article  CAS  PubMed  Google Scholar 

  22. Ferreira R, Ohneda K, Yamamoto M, Philipsen S (2005) GATA1 function, a paradigm for transcription factors in hematopoiesis. Mol Cell Biol 25:1215–1227

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Stachura DL, Chou ST, Weiss MJ (2006) Early block to erythromegakaryocytic development conferred by loss of transcription factor GATA-1. Blood 107:87–97

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  24. Bultsma Y, Keune WJ, Divecha N (2010) PIP4Kbeta interacts with and modulates nuclear localization of the high-activity PtdIns5P-4-kinase isoform PIP4Kalpha. Biochem J 430:223–235

    Article  CAS  PubMed  Google Scholar 

  25. Luoh SW, Venkatesan N, Tripathi R (2004) Overexpression of the amplified Pip4k2beta gene from 17q11-12 in breast cancer cells confers proliferation advantage. Oncogene 23:1354–1363

    Article  CAS  PubMed  Google Scholar 

  26. Clarke JH, Richardson JP, Hinchliffe KA, Irvine RF (2007) Type II PtdInsP kinases: location, regulation and function. Biochem Soc Symp 74:149–159

    Article  CAS  PubMed  Google Scholar 

  27. Wang M, Bond NJ, Letcher AJ, Richardson JP, Lilley KS, Irvine RF, Clarke JH (2010) Genomic tagging reveals a random association of endogenous PtdIns5P 4-kinases IIalpha and IIbeta and a partial nuclear localization of the IIalpha isoform. Biochem J 430:215–221

    Article  CAS  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgments

The authors would like to thank Tereza Salles for her valuable technical assistance and the National Institute of Science and Technology for Photonics Applied to Cell Biology (INFABIC) for providing access to equipment and assistance. This work received financial support from the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenadoria de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) and Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), Brazil.

Conflict of interest

The authors have no conflict of interest to report.

Author information

Authors and Affiliations

  1. Department of Clinical Pathology, School of Medical Sciences, University of Campinas - UNICAMP, P.O. Box 6111, Campinas, São Paulo, 13083-970, Brazil

    Vânia Peretti de Albuquerque Wobeto, Tânia Regina Zaccariotto, Daniela Maria Ribeiro & Maria de Fatima Sonati

  2. Hematology and Hemotherapy Center, Instituto Nacional de Ciência e Tecnologia do Sangue, University of Campinas - UNICAMP, Campinas, São Paulo, Brazil

    João Agostinho Machado-Neto, Adriana da Silva Santos Duarte, Sara Teresinha Olalla Saad & Fernando Ferreira Costa

Authors
  1. Vânia Peretti de Albuquerque Wobeto
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. João Agostinho Machado-Neto
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tânia Regina Zaccariotto
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Daniela Maria Ribeiro
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Adriana da Silva Santos Duarte
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Sara Teresinha Olalla Saad
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Fernando Ferreira Costa
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Maria de Fatima Sonati
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Maria de Fatima Sonati.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Peretti de Albuquerque Wobeto, V., Machado-Neto, J.A., Zaccariotto, T.R. et al. PIPKIIα is widely expressed in hematopoietic-derived cells and may play a role in the expression of alpha- and gamma-globins in K562 cells. Mol Cell Biochem 393, 145–153 (2014). https://doi.org/10.1007/s11010-014-2054-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-014-2054-y

Keywords

Search

Navigation