Cell and Tissue Research

, Volume 344, Issue 2, pp 189–205 | Cite as

Protein tyrosine phosphatase interacting protein 51—a jack-of-all-trades protein

  • Alexander Brobeil
  • Manuel Bobrich
  • Monika WimmerEmail author
At-a-Glance Article


Protein tyrosine phosphatase interacting protein 51 (PTPIP51) interacts both in vitro and in vivo with PTP1B, a protein tyrosine phosphatase involved in cellular regulation. PTPIP51 is known to be expressed in many different types of tissues. It is involved in cellular processes such as proliferation, differentiation and apoptosis. Nevertheless, the exact cellular function of PTPIP51 is still unknown. The present review summarizes our current knowledge of the PTPIP51 gene and its mRNA and protein structure.


PTPIP51 Gene regulation mRNA structure Protein domains Isoforms 



We thank the native speaker Mr. Phillip Grant (Department of Differential Psychology and Personality Research, Justus Liebig University, Gießen) for excellent linguistic revision.


  1. Azadi S, Johnson LE, Paquet-Durand F, Perez MT, Zhang Y, Ekström PA, Van Veen T (2007) CNTF + BDNF treatment and neuroprotective pathways in the rd1 mouse retina. Brain Res 1129:116–129PubMedCrossRefGoogle Scholar
  2. Barop J, Sauer H, Steger K, Wimmer M (2009) Differentiation-dependent PTPIP51 expression in human skeletal muscle cell culture. J Histochem Cytochem 57:425–435PubMedCrossRefGoogle Scholar
  3. Barreda DR, Hanington PC, Belosevic M (2004) Regulation of myeloid development and function by colony stimulating factors. Dev Comp Immunol 28:509–554PubMedCrossRefGoogle Scholar
  4. Blatch GL, Lässle M (1999) The tetratricopeptide repeat: a structural motif mediating protein-protein interactions. Bioessays 21:932–939PubMedCrossRefGoogle Scholar
  5. Bobrich M, Brobeil A, Mooren FC, Krüger K, Steger K, Wimmer M (2011) PTPIP51 interaction with PTP1B and 14-3-3beta in adipose tissue of insulin resistant mice. Int J Obes (Lond) [Epub ahead of print]Google Scholar
  6. Bonizzoni P, Rizzi R, Pesole G (2005) ASPIC: a novel method to predict the exon-intron structure of a gene that is optimally compatible to a set of transcript sequences. BMC Bioinform 6:244CrossRefGoogle Scholar
  7. Brobeil A, Graf M, Oeschger S, Steger K, Wimmer M (2010) PTPIP51-a myeloid lineage specific protein interacts with PTP1B in neutrophil granulocytes. Blood Cells Mol Dis 45:159–168PubMedCrossRefGoogle Scholar
  8. Calarco JA, Superina S, O’Hanlon D, Gabut M, Raj B, Pan Q, Skalska U, Clarke L, Gelinas D, Van der Kooy D, Zhen M, Ciruna B, Blencowe BJ (2009) Regulation of vertebrate nervous system alternative splicing and development by an SR-related protein. Cell 138:898–910PubMedCrossRefGoogle Scholar
  9. Cantin GT, Yi W, Lu B, Park SK, Xu T, Lee JD, Yates JR 3rd (2008) Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis. J Proteome Res 7:1346–1351PubMedCrossRefGoogle Scholar
  10. Daub H, Olsen JV, Bairlein M, Gnad F, Oppermann FS, Körner R, Greff Z, Kéri G, Stemmann O, Mann M (2008) Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle. Mol Cell 31:438–448PubMedCrossRefGoogle Scholar
  11. Davuluri RV, Suzuki Y, Sugano S, Plass C, Huang TH (2008) The functional consequences of alternative promoter use in mammalian genomes. Trends Genet 24:167–177PubMedCrossRefGoogle Scholar
  12. De Almeida LP, Zala D, Aebischer P, Déglon N (2001) Neuroprotective effect of a CNTF-expressing lentiviral vector in the quinolinic acid rat model of Huntington’s disease. Neurobiol Dis 8:433–446PubMedCrossRefGoogle Scholar
  13. Delgehyr N, Sillibourne J, Bornens M (2005) Microtubule nucleation and anchoring at the centrosome are independent processes linked by ninein function. J Cell Sci 118:1565–1575PubMedCrossRefGoogle Scholar
  14. DeLuca JG, Moree B, Hickey JM, Kilmartin JV, Salmon ED (2002) hNuf2 inhibition blocks stable kinetochore-microtubule attachment and induces mitotic cell death in HeLa cells. J Cell Biol 159:549–555PubMedCrossRefGoogle Scholar
  15. Dephoure N, Zhou C, Villén J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP (2008) A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci USA 105:10762–10767PubMedCrossRefGoogle Scholar
  16. De Virgilio C, Pousis C, Bruno S, Gadaleta G (2011) New isoforms of human mitochondrial transcription factor A detected in normal and tumoral cells. Mitochondrion 11:287–295PubMedCrossRefGoogle Scholar
  17. Ellis L, Atadja PW, Johnstone RW (2009) Epigenetics in cancer: targeting chromatin modifications. Mol Cancer Ther 8:1409–1420PubMedCrossRefGoogle Scholar
  18. Fotheringham AP, Davidson YS, Davies I, Morris JA (1991) Age-associated changes in neuroaxonal transport in the hypothalamo-neurohypophysial system of the mouse. Mech Ageing Dev 60:113–121PubMedCrossRefGoogle Scholar
  19. Gan HK, Kaye AH, Luwor RB (2009) The EGFRvIII variant in glioblastoma multiforme. J Clin Neurosci 16:748–754PubMedCrossRefGoogle Scholar
  20. Gillingham AK, Munro S (2003) Long coiled-coil proteins and membrane traffic. Biochim Biophys Acta 1641:71–85PubMedCrossRefGoogle Scholar
  21. Goebl M, Yanagida M (1991) The TPR snap helix: a novel protein repeat motif from mitosis to transcription. Trends Biochem Sci 16:173–177PubMedCrossRefGoogle Scholar
  22. Heinonen KM, Tremblay ML (2006) Protein tyrosine phosphatase 1B in hematopoiesis. Cell Cycle 5:1053–1056PubMedCrossRefGoogle Scholar
  23. Howng SL, Hsu HC, Cheng TS, Lee YL, Chang LK, Lu PJ, Hong YR (2004) A novel ninein-interaction protein, CGI-99, blocks ninein phosphorylation by GSK3beta and is highly expressed in brain tumors. FEBS Lett 566:162–168PubMedCrossRefGoogle Scholar
  24. Jin J, Smith FD, Stark C, Wells CD, Fawcett JP, Kulkarni S, Metalnikov P, O’Donnell P, Taylor P, Taylor L, Zougman A, Woodgett JR, Langeberg LK, Scott JD, Pawson T (2004) Proteomic, functional, and domain-based analysis of in vivo 14-3-3 binding proteins involved in cytoskeletal regulation and cellular organization. Curr Biol 14:1436–1450PubMedCrossRefGoogle Scholar
  25. Klumpp S, Krieglstein J (2002) Serine/threonine protein phosphatases in apoptosis. Curr Opin Pharmacol 2:458–462PubMedCrossRefGoogle Scholar
  26. Koch P, Stenzinger A, Viard M, Märker D, Mayser P, Nilles M, Schreiner D, Steger K, Wimmer M (2008) The novel protein PTPIP51 is expressed in human keratinocyte carcinomas and their surrounding stroma. J Cell Mol Med 12:2083–2095PubMedCrossRefGoogle Scholar
  27. Koch P, Petri M, Paradowska A, Stenzinger A, Sturm K, Steger K, Wimmer M (2009a) PTPIP51 mRNA and protein expression in tissue microarrays and promoter methylation of benign prostate hyperplasia and prostate carcinoma. Prostate 69:1751–1762CrossRefGoogle Scholar
  28. Koch P, Viard M, Stenzinger A, Brobeil A, Tag C, Steger K, Wimmer M (2009b) Expression profile of PTPIP51 in mouse brain. J Comp Neurol 517:892–905CrossRefGoogle Scholar
  29. Kochetov AV (2008) Alternative translation start sites and hidden coding potential of eukaryotic mRNAs. Bioessays 30:683–691PubMedCrossRefGoogle Scholar
  30. Kozak M (2005) Regulation of translation via mRNA structure in prokaryotes and eukaryotes. Gene 361:13–37PubMedCrossRefGoogle Scholar
  31. Lessard L, Stuible M, Tremblay ML (2010) The two faces of PTP1B in cancer. Biochim Biophys Acta 1804:613–619PubMedGoogle Scholar
  32. Linden R, Martins RA, Silveira MS (2005) Control of programmed cell death by neurotransmitters and neuropeptides in the developing mammalian retina. Prog Retin Eye Res 24:457–491PubMedCrossRefGoogle Scholar
  33. Lv BF, Yu CF, Chen YY, Lu Y, Guo JH, Song QS, Ma DL, Shi TP, Wang L (2006) Protein tyrosine phosphatase interacting protein 51 (PTPIP51) is a novel mitochondria protein with an N-terminal mitochondrial targeting sequence and induces apoptosis. Apoptosis 11:1489–1501PubMedCrossRefGoogle Scholar
  34. Ly JD, Grubb DR, Lawen A (2003) The mitochondrial membrane potential (deltapsi(m)) in apoptosis; an update. Apoptosis 8:115–128PubMedCrossRefGoogle Scholar
  35. Lynch KW (2007) Regulation of alternative splicing by signal transduction pathways. Adv Exp Med Biol 623:161–174PubMedCrossRefGoogle Scholar
  36. Maerker D, Stenzinger A, Schreiner D, Tag C, Wimmer M (2008) Expression of PTPIP51 during mouse eye development. Histochem Cell Biol 129:345–356PubMedCrossRefGoogle Scholar
  37. McCubrey JA, May WS, Duronio V, Mufson A (2000) Serine/threonine phosphorylation in cytokine signal transduction. Leukemia 14:9–21PubMedCrossRefGoogle Scholar
  38. Miranda MB, Johnson DE (2007) Signal transduction pathways that contribute to myeloid differentiation. Leukemia 21:1363–1377PubMedCrossRefGoogle Scholar
  39. Morin PJ (1999) Beta-catenin signaling and cancer. Bioessays 21:1021–1030PubMedCrossRefGoogle Scholar
  40. Nilsen TW, Graveley BR (2010) Expansion of the eukaryotic proteome by alternative splicing. Nature 463:457–463PubMedCrossRefGoogle Scholar
  41. Oishi K, Okano H, Sawa H (2007) RMD-1, a novel microtubule-associated protein, functions in chromosome segregation in Caenorhabditis elegans. J Cell Biol 179:1149–1162 [Erratum in: J Cell Biol (2009) 186:629]PubMedCrossRefGoogle Scholar
  42. Onuma H, Osawa H, Yamada K, Ogura T, Tanabe F, Granner DK, Makino H (2002) Identification of the insulin-regulated interaction of phosphodiesterase 3B with 14-3-3 beta protein. Diabetes 51:3362–3367PubMedCrossRefGoogle Scholar
  43. Peters KL, Smithgall TE (1999) Tyrosine phosphorylation enhances the SH2 domain-binding activity of Bcr and inhibits Bcr interaction with 14-3-3 proteins. Cell Signal 11:507–514PubMedCrossRefGoogle Scholar
  44. Qi X, Mochly-Rosen D (2008) The PKCdelta-Abl complex communicates ER stress to the mitochondria—an essential step in subsequent apoptosis. J Cell Sci 121:804–813PubMedCrossRefGoogle Scholar
  45. Rieder CL, Faruki S, Khodjakov A (2001) The centrosome in vertebrates: more than a microtubule-organizing center. Trends Cell Biol 11:413–419PubMedCrossRefGoogle Scholar
  46. Robinson K, Jones D, Patel Y, Martin H, Madrazo J, Martin S, Howell S, Elmore M, Finnen MJ, Aitken A (1994) Mechanism of inhibition of protein kinase C by 14-3-3 isoforms. 14-3-3 isoforms do not have phospholipase A2 activity. Biochem J 299:853–861PubMedGoogle Scholar
  47. Roger J, Goureau O, Sahel JA, Guillonneau X (2007) Use of suppression subtractive hybridization to identify genes regulated by ciliary neurotrophic factor in postnatal retinal explants. Mol Vis 13:206–219PubMedGoogle Scholar
  48. Rose A, Meier I (2004) Scaffolds, levers, rods and springs: diverse cellular functions of long coiled-coil proteins. Cell Mol Life Sci 61:1996–2009PubMedCrossRefGoogle Scholar
  49. Roy A, Kucukural A, Zhang Y (2010) I-TASSER: a unified platform for automated protein structure and function prediction. Nat Protoc 5:725–738PubMedCrossRefGoogle Scholar
  50. Russell JA, Leng G (2000) Veni, vidi, vici: the neurohypophysis in the twentieth century. Exp Physiol 85:1–6CrossRefGoogle Scholar
  51. Sánchez L (2008) Sex-determining mechanisms in insects. Int J Dev Biol 52:837–856PubMedCrossRefGoogle Scholar
  52. Saraste A, Pulkki K (2000) Morphologic and biochemical hallmarks of apoptosis. Cardiovasc Res 45:528–537PubMedCrossRefGoogle Scholar
  53. Shames DS, Minna JD, Gazdar AF (2007) DNA methylation in health, disease, and cancer. Curr Mol Med 7:85–102PubMedCrossRefGoogle Scholar
  54. Shaul Y, Ben-Yehoyada M (2005) Role of c-Abl in the DNA damage stress response. Cell Res 15:33–35PubMedCrossRefGoogle Scholar
  55. Shaywitz AJ, Greenberg ME (1999) CREB: a stimulus-induced transcription factor activated by a diverse array of extracellular signals. Annu Rev Biochem 68:821–861PubMedCrossRefGoogle Scholar
  56. Sikorski RS, Boguski MS, Goebl M, Hieter P (1990) A repeating amino acid motif in CDC23 defines a family of proteins and a new relationship among genes required for mitosis and RNA synthesis. Cell 60:307–317PubMedCrossRefGoogle Scholar
  57. Sirvent A, Benistant C, Roche S (2008) Cytoplasmic signalling by the c-Abl tyrosine kinase in normal and cancer cells. Biol Cell 100:617–631PubMedCrossRefGoogle Scholar
  58. Stenzinger A, Kajosch T, Tag C, Porsche A, Welte I, Hofer HW, Steger K, Wimmer M (2005) The novel protein PTPIP51 exhibits tissue- and cell-specific expression. Histochem Cell Biol 123:19–28PubMedCrossRefGoogle Scholar
  59. Stenzinger A, Schreiner D, Pfeiffer T, Tag C, Hofer HW, Wimmer M (2006) Epidermal growth factor-, transforming growth factor-beta-, retinoic acid- and 1, 25-dihydroxyvitamin D3-regulated expression of the novel protein PTPIP51 in keratinocytes. Cells Tissues Organs 184:76–87PubMedCrossRefGoogle Scholar
  60. Stenzinger A, Schreiner D, Tag C, Wimmer M (2007) Expression of the novel protein PTPIP51 in rat liver: an immunohistochemical study. Histochem Cell Biol 128:77–84PubMedCrossRefGoogle Scholar
  61. Stenzinger A, Märker D, Koch P, Hoffmann J, Baal N, Steger K, Wimmer M (2009a) Protein tyrosine phosphatase interacting protein 51 (PTPIP51) mRNA expression and localization and its in vitro interacting partner protein tyrosine phosphatase 1B (PTP1B) in human placenta of the first, second, and third trimester. J Histochem Cytochem 57:143–153CrossRefGoogle Scholar
  62. Stenzinger A, Schreiner D, Koch P, Hofer HW, Wimmer M (2009b) Cell and molecular biology of the novel protein tyrosine-phosphatase-interacting protein 51. Int Rev Cell Mol Biol 275:183–246CrossRefGoogle Scholar
  63. Tan Y, Demeter MR, Ruan H, Comb MJ (2000) BAD Ser-155 phosphorylation regulates BAD/Bcl-XL interaction and cell survival. J Biol Chem 275:25865–25869PubMedCrossRefGoogle Scholar
  64. Xiang X, Yuan M, Song Y, Ruderman N, Wen R, Luo Z (2002) 14-3-3 facilitates insulin-stimulated intracellular trafficking of insulin receptor substrate 1. Mol Endocrinol 3:552–562CrossRefGoogle Scholar
  65. Xue Y, Ren J, Gao X, Jin C, Wen L, Yao X (2008) GPS 2.0, a tool to predict kinase-specific phosphorylation sites in hierarchy. Mol Cell Proteomics 7:1598–1608PubMedCrossRefGoogle Scholar
  66. Yoshida K (2007a) Regulation for nuclear targeting of the Abl tyrosine kinase in response to DNA damage. Adv Exp Med Biol 604:155–165CrossRefGoogle Scholar
  67. Yoshida K (2007b) PKCdelta signaling: mechanisms of DNA damage response and apoptosis. Cell Signal 19:892–901CrossRefGoogle Scholar
  68. Yu C, Han W, Shi T, Lv B, He Q, Zhang Y, Li T, Zhang Y, Song Q, Wang L, Ma D (2008) PTPIP51, a novel 14-3-3 binding protein, regulates cell morphology and motility via Raf-ERK pathway. Cell Signal 20:2208–2220PubMedCrossRefGoogle Scholar
  69. Zhang X, Odom DT, Koo SH, Conkright MD, Canettieri G, Best J, Chen H, Jenner R, Herbolsheimer E, Jacobsen E, Kadam S, Ecker JR, Emerson B, Hogenesch JB, Unterman T, Young RA, Montminy M (2005) Genome-wide analysis of cAMP-response element binding protein occupancy, phosphorylation, and target gene activation in human tissues. Proc Natl Acad Sci USA 102:4459–4464PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Alexander Brobeil
    • 1
  • Manuel Bobrich
    • 1
  • Monika Wimmer
    • 1
    Email author
  1. 1.Institute of Anatomy and Cell BiologyJustus-Liebig-UniversityGiessenGermany

Personalised recommendations