DOI QR코드

DOI QR Code

The EphA8 Receptor Phosphorylates and Activates Low Molecular Weight Phosphotyrosine Protein Phosphatase in Vitro

  • Park, Soo-Chul (Department of Life Science, Sookmyung Women's University)
  • Received : 2003.01.20
  • Accepted : 2003.03.03
  • Published : 2003.05.31

Abstract

Low molecular weight phosphotyrosine protein phosphatase (LMW-PTP) has been implicated in modulating the EphB1-mediated signaling pathway. In this study, we demonstrated that the EphA8 receptor phosphorylates LMW-PTP in vitro. In addition, we discovered that mixing these two proteins leads to EphA8 dephosphorylation in the absence of phosphatase inhibitors. Finally, we demonstrated that LMW-PTP, modified by the EphA8 autokinase activity, possesses enhanced catalytic activity in vitro. These results suggest that LMW-PTP may also participate in a feedback-control mechanism of the EphA8 receptor autokinase activity in vivo.

Keywords

References

  1. Berti, A., Rigacci, S., Raugei, G., Degl'Innocenti, D. and Ramponi, G. (1994) Inhibition of cellular response to platelet-derived growth factor by low M(r) phosphotyrosine protein phosphatase overexpression. FEBS Lett. 349, 7-12. https://doi.org/10.1016/0014-5793(94)00620-2
  2. Chiarugi, P., Marzocchini, R., Raugei, G., Pazzagli, C., Berti, A., Camici, G., Manao, G., Cappugi, G. and Ramponi, G. (1992) Differential role of four cysteines on the activity of a low M(r) phosphotyrosine protein phosphatase. FEBS Lett. 310, 9-12. https://doi.org/10.1016/0014-5793(92)81134-8
  3. Choi, S. and Park, S. (1999) Phosphorylation at Tyr-838 in the kinase domain of EphA8 modulates Fyn binding to the Tyr-615 site by enhancing tyrosine kinase activity. Oncogene 18, 5413-5422. https://doi.org/10.1038/sj.onc.1202917
  4. Cirri, P., Chiarugi, P., Camici, G., Manao, G., Raugei, G., Cappugi, G. and Ramponi, G. (1993) The role of Cys12, Cys17 and Arg18 in the catalytic mechanism of low-M(r) cytosolic phosphotyrosine protein phosphatase. Eur. J. Biochem. 214, 647-657, https://doi.org/10.1111/j.1432-1033.1993.tb17965.x
  5. Davy, A., Gale, N. W., Murray, E. W., Klinghoffer, R. A., Soriano, P., Feuerstein, C. and Robbins, S. M. (1999) Compartmentalized signaling by GPI-anchored ephrin-A5 requires the Fyn tyrosine kinase to regulate cellular adhesion. Genes Dev. 13, 3125-3135. https://doi.org/10.1101/gad.13.23.3125
  6. Dodelet, V. C., Pazzagli, C., Zisch, A. H., Hauser, C. A. and Pasquale, E. B. (1999) A novel signaling intermediate, SHEP1, directly couples Eph receptors to R-Ras and Rap1A. J. BioI. Chem. 274, 31941-31946. https://doi.org/10.1074/jbc.274.45.31941
  7. Elowe, S., Holland, S. J., Kulkarni, S. and Pawson, T. (2001) Downregulation of the Ras-mitogen-activated protein kinase pathway by the EphB2 receptor tyrosine kinase is required for ephrin-induced neurite retraction. Mol. Cell. Biol. 21, 7429-7441. https://doi.org/10.1128/MCB.21.21.7429-7441.2001
  8. Eph Nomenclature Committee. (1997) Unified nomenclature for Eph family receptors and their ligands, the ephrins. Cell 90, 403-404, https://doi.org/10.1016/S0092-8674(00)80500-0
  9. Flanagan, J. G. and Vanderhaeghen, P. (1998) The ephrins and Eph receptors in neural development. Annu. Rev. Neurosci. 21, 309-345, https://doi.org/10.1146/annurev.neuro.21.1.309
  10. Graham, F. L. and van der Eb. A. J. (1973) Transformation of rat cells by DNA of human adenovirus 5. Virology 54, 536-539. https://doi.org/10.1016/0042-6822(73)90163-3
  11. Gu, C. and Park, S. (2001) The EphA8 receptor regulates integrin activity through p110gamma phosphatidylinositol-3 kinase in a tyrosine kinase activity-independent manner. Mol. Cell. Biol. 21, 4579-4597. https://doi.org/10.1128/MCB.21.14.4579-4597.2001
  12. Huai, J, and Drescher, U. (2001) An ephrin-A-dependent signaling pathway controls integrin function and is linked to the tyrosine phosphorylation of a 120-kDa protein. J. Biol. Chem. 276, 6689-6694. https://doi.org/10.1074/jbc.M008127200
  13. Huynh-Do, U., Stein, E., Lane, A. A., Liu, H., Cerretti, D. P. and Daniel, T. O. (1999) Surface densities of ephrin-B1 determine EphB1-coupled activation of cell attachment through alphavbeta3 and alpha5beta1 integrins. EMBO J. 18, 2165-2173. https://doi.org/10.1093/emboj/18.8.2165
  14. Kim, Y. S., Ha, K. S., Kim, Y. H. and Bae, Y. S. (2002) The Ring-H2 finger motif of CKBBP1/SAG is necessary for interaction with protein kinase CKII and optimal cell proliferation. J. Biochem. Mol. Biol. 35, 629-636. https://doi.org/10.5483/BMBRep.2002.35.6.629
  15. Knoll, B., Zarbalis, K., Wurst, W. and Drescher, U. (2001) A role for the EphA family in the topographic targeting of vomeronasal axons. Development 128, 895-906.
  16. Mellitzer, G., Xu, Q. and Wilkinson, D. G. (2000) Control of cell behavior by signaling through Eph receptors and ephrins. Curr. Opin. Neurobiol. 10, 400-408. https://doi.org/10.1016/S0959-4388(00)00095-7
  17. Menzel, P., Valencia, F., Godement, P., Dodelet, V. C. and Pasquale, E. B. (2001) Ephrin-A6, a new ligand for EphA receptors in the developing visual system. Dev. BioI. 230, 74-88. https://doi.org/10.1006/dbio.2000.0109
  18. Miao, H., Burnett, E., Kinch, M., Simon, E. and Wang, B. (2000) Activation of EphA2 kinase suppresses integrin function and causes focal-adhesion-kinase dephosphorylation. Nat. Cell Biol. 2, 62-69. https://doi.org/10.1038/35000008
  19. Ramponi, G., Manao, G., Camici, G., Cappugi, G., Ruggiero, M. and Botturo, D. P. (1989) The 18 kDa cytosolic acid phosphatase from bovine live has phosphotyrosine phosphatase activity on the autophosphorylated epidermal growth factor receptor. FEBS Lett. 250, 469-473 https://doi.org/10.1016/0014-5793(89)80778-1
  20. Rigacci, S., Degl'Innocenti, D., Bucciantini, M., Cirri. P., Berti, A. and Ramponi, G. (1996) pp60v-src phosphorylates and activates low molecular weight phosphotyrosine-protein phosphatase. J. Biol. Chem. 271, 1278-1281. https://doi.org/10.1074/jbc.271.3.1278
  21. Shamah, S. M., Lin, M. Z., Goldberg, J. L., Estrach, S., Sahin, M., Hu, L., Bazalakova, M., Neve, R. L., Corfas, G., Debant, A. and Greenberg, M. E. (2001) EphA receptors regulate growth cone dynamics through the novel guanine nucleotide exchange factor ephexin. Cell 105, 233-244. https://doi.org/10.1016/S0092-8674(01)00314-2
  22. Stein, E., Huynh-Do, U., Lane, A. A., Cerretti, D. P. and Daniel, T. O. (1988a) Nck recruitment to Eph receptor, EphB1/ELK, couples ligand activation to c-Jun kinase. J. Biol. Chem. 273, 1303-1308. https://doi.org/10.1074/jbc.273.3.1303
  23. Stein, E., Lane, A. A., Cerretti, D. P., Schoecklmann, H. O., Schroff, A. D., Van Etten, R. L. and Daniel, T. O. (1998b) Eph receptors discriminate specific ligand oligomers to determine alternative signaling complexes, attachment, and assembly responses. Genes Dev. 12, 667-678. https://doi.org/10.1101/gad.12.5.667
  24. Wahl, S., Barth, H., Ciossek. T., Aktories, K. and Mueller, B. K. (2000) Ephrin-A5 induces collapse of growth cones by activating Rho and Rho kinase. J. Cell BioI. 149, 263-270. https://doi.org/10.1083/jcb.149.2.263
  25. Yi, J. Y., Hong, W. S. and Son, Y. S. (2001) Biochemical characterization of adriamycin-resistance in PC-14 human lung adenocarcinoma cell line, J. Biochem. Mol. Biol. 34, 66-72.
  26. Zou, J. X., Wang, B., Kalo, M. S., Zisch, A. H., Pasquale, E. B. and Ruoslallti, E. (1999) An Eph receptor regulates integrin activity through R-Ras. Proc. Natl. Acad. Sci. USA 96, 13813-13818. https://doi.org/10.1073/pnas.96.24.13813

Cited by

  1. Elevated protein tyrosine phosphatase activity provokes Eph/ephrin-facilitated adhesion of pre-B leukemia cells vol.112, pp.3, 2008, https://doi.org/10.1182/blood-2007-11-121681