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PH Domain of Serine-Threonine Protein Kinase B (RAC-PKB)

Expression and Binding Assay for Phosphoinositides and Inositol Phosphates
  • Matthias Frech
  • Brian A. Hemmings
Part of the Methods in Molecular Biology™ book series (MIMB, volume 88)

Abstract

The Pleckstrin homology (PH) domain, as a recent newcomer to the family of protein modules involved in signal transduction, has attracted great interest (1, 2, 3). The PH domain was first recognized as an internal repeat in pleckstrin, the major substrate of protein kinase C in activated platelets (4). Initially overlooked because of the very low sequence similarity between the different PH domains, presently over 90 proteins are known to possess PH domains (5, 6, 7, 8, 9). This domain is often found in proteins involved in signal transduction or cytoskeletal function and forms an independent folding domain of about 100 amino acids. Despite of the very low similarity, their three-dimensional structures are highly related. Several structures of isolated PH domains derived from different proteins are known: pleckstrin (10), dynamin (11, 12, 13, 14), β-spectrin (15, 16, 17), and phospholipaseCδ-1 (18).

Keywords

Phosphate Group Tryptophan Residue Inositol Phosphate Pleckstrin Homology Pleckstrin Homology Domain 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Haslam, R. J., Koide, H. B., and Hemmings, B. A. (1993) Pleckstrin domain homology. Nature 363, 310,311.CrossRefGoogle Scholar
  2. 2.
    Mayer, B. J., Ren, R., Clark, K. L., and Baltimore, D. (1993) A putative modular domain present in diverse signaling proteins. Cell 73, 629,630.PubMedCrossRefGoogle Scholar
  3. 3.
    Musacchio, A., Gibson, T., Rice, P., Thompsen, J., and Saraste, M. (1993) The PH domain: a common piece in the structural patchwork of signalling proteins. Trends Biochem. Sci. 18, 343–348.PubMedCrossRefGoogle Scholar
  4. 4.
    Tyers, M., Rachubinski, R. A., Stewart, M. I., Varrichio, A. M., Shorr, R. G. L., Haslam, R. J., and Harley, C. B. (1988) Molecular cloning and expression of the major protein kinase C substrate of platelets. Nature 333, 470–473.PubMedCrossRefGoogle Scholar
  5. 5.
    Shaw, G. (1993) Identification of novel Pleckstrin homology (PH) domains provides a hypothesis for PH domain function. Biochem. Biophys. Res. Commun. 195, 1145–1151.PubMedCrossRefGoogle Scholar
  6. 6.
    Gibson, T. J., Hyvönen, M., Musachio, A., Saraste, M., and Birney, E. (1994) PH domain: the first anniversary. Trend Biochem. Sci. 19, 349–353.PubMedCrossRefGoogle Scholar
  7. 7.
    Ingley, E. and Hemmings, B. A. (1994) Pleckstrin homology (PH) domains in signal transduction. J. Cell. Biochem. 58, 1–8.Google Scholar
  8. 8.
    Saraste, M. and Hyvönen, M. (1995) PH domains: a fact file. Curr. Opin. Struct. Biol. 5, 403–408.PubMedCrossRefGoogle Scholar
  9. 9.
    Parker, P. J., Hemmings, B. A., and Gierschik, P. (1994) PH domains and phospholipases—a meaning relationship? Trends Biochem. Sci. 19, 54,55.PubMedCrossRefGoogle Scholar
  10. 10.
    Yoon, H. S., Hajduk, P. J., Petros, A. M., Olejniczak, E. T., Meadows, R. P., and Fesik, S. W. (1994) Solution structure of a pleckstrin-homology domain. Nature 369, 672–675.PubMedCrossRefGoogle Scholar
  11. 11.
    Downing, A. K., Driscoll, P. C., Gout, I., Salim, K., Zvelebil, M. J., and Waterfield, M. D. (1994) Three-dimensional solution structure of the pleckstrin homology domain from dynamin. Curr. Biol. 4, 884–891.PubMedCrossRefGoogle Scholar
  12. 12.
    Ferguson, K. M., Lemmon, M. A., Schlessinger, J., and Sigler, P. B. (1994) Crystal structure at 2. 2 Å resolution of the pleckstrin homology domain from human dynamin. Cell 79, 199–209.PubMedCrossRefGoogle Scholar
  13. 13.
    Fushman, D., Cahill, S., Lemmon, M. A., Schlessinger, J., and Cowburn, D. (1994) Solution structure of pleckstrin homology domain of dynamin by heteronuclear NMR spectroscopy. Proc. Natl. Acad. Sci. USA 92, 816–820.CrossRefGoogle Scholar
  14. 14.
    Timm, D., Salim, K., Gout, I., Guruprasad, L., Waterfield, M., and Blundell, T. (1994) Crystal structure of the pleckstrin homology domain from dynamin. Structural Biol. 1, 782–788.CrossRefGoogle Scholar
  15. 15.
    Macias, M. J., Musacchio, A., Ponstingl, H., Nilges, M., Saraste, M., and Oschkinat, H. (1994) Structure of the pleckstrin homology domain of β-spectrin. Nature 369, 675–677.PubMedCrossRefGoogle Scholar
  16. 16.
    Hyvönen, M, Macias, J. M., Nilges, M., Oschkinat, H., Saraste, M., and Wilmans, M. (1995) Structure of the binding site for inositol phosphates in a PH domain. EMBO 14, 4676–4685.Google Scholar
  17. 17.
    Zhang, P., Talluri, S., Deng, H., Branton, D., and Wagner, G. (1995) Solution structure of the pleckstrin homology domain of Drosophila β-spectrin. Structure 3, 1185–1195.PubMedCrossRefGoogle Scholar
  18. 18.
    Ferguson, K. M., Lemmon, M. A., Schlessinger, J., and Sigler, P. B. (1995) Structure of the high affinity complex of inositol trisphosphate with a Phospholipase C pleckstrin homology domain. Cell 83, 1037–1046.PubMedCrossRefGoogle Scholar
  19. 19.
    Tsukada, S., Saffran, D. C., Rawlings, D. J., Parolini, O., Allen, R. C., Klisak, I., Sparkes, R. S., Kubagawa, H. Mohandas, T., Quan, S., Belmont, J. W., Cooper, M. D., Conley, M. E., and Witte, O. N. (1993) Deficient expression of a B cell cytoplasmic tyrosine kinase in human X-linked agammaglobulinemia. Cell 72, 279–290.PubMedCrossRefGoogle Scholar
  20. 20.
    Vetrie, D., Vorechovsky, I., Sideras, P., Holland, J., Davies, A., Flinter, F. Hammarstrom, L. Kinnon, C., Levinsky, R., Bobrow, M., Smith, C. I. E., and Bentley, D. R. (1993) The gene involved in X-linked agammaglobulinaemia is a member of the src familiy of protein-tyrosine kinases. Nature 361, 226–233.PubMedCrossRefGoogle Scholar
  21. 21.
    Rawlings, D. J., Saffran, D. C., Tsukada, S., Largaespada, D. A., Grimaldi, J. C., Cohen, L., Mohr, R. N., Bazan, J. F., Howard, M., Copeland, N. G., Jenkins, N. A., and Witte, O. N. (1993) Mutation of unique region of Bruton’s tyrosine kinase in immunodeficient XID mice. Science 261, 358–361.PubMedCrossRefGoogle Scholar
  22. 22.
    Thomas, J. D., Sideras, P., Smith, C. I. E., Vorechovsky, I., Chapman, V., and Paul, W. E. (1993) Colocalization of X-linked agammaglobulinemia and X-linked immunodeficiency genes. Science 261, 355–358.PubMedCrossRefGoogle Scholar
  23. 23.
    Myers, M. G., Grammer, T. C., Brooks, J., Glasheen, E. M., Wang, L.-M., Sun, X. J., Blenis, J., Pierce, J. H., and White, M. F. (1995) The pleckstrin homology domain in insulin receptor substrate-1 sensitizes insulin signaling. J. Biol. Chem. 270, 11,715–11,718.PubMedCrossRefGoogle Scholar
  24. 24.
    Voliovitch, H., Schindler, D. G., Hadari, Y. R., Taylor, S. I., Accili, D., and Zick, Y. (1995) Tyrosine phosphorylation of insulin receptor substrate-1 in vivo depends upon the presence of its pleckstrin homology region. J. Biol. Chem. 270, 18,083–18,087.PubMedCrossRefGoogle Scholar
  25. 25.
    Datta, K., Franke, T. F., Chan, T. O., Makris, A., Yang, S.-I., Kaplan, D. R., Morrison, D. K., Golemis, E. A., and Tsichlis, P. N. (1995) AH/PH domain-mediated interaction between Akt molecules and its potential role in Akt regulation. Mol. Cell. Biol. 15, 2304–2310.PubMedGoogle Scholar
  26. 26.
    Franke, T. F., Yang, S.-I., Chan, T. O., Datta, K., Kazlaukas, A., Morrison, D. K., Kaplan, D. R., and Tsichlis, P. N. (1995) The protein kinase encoded by the Akt proto-oncogene is a target of the PDGF-activated phosphatidylinositol 3-Kinase. Cell 81, 727–736.PubMedCrossRefGoogle Scholar
  27. 27.
    Kohn, A. D., Kovacina, K. S., and Roth, R. A. (1995) Insulin stimulates the kinase activity of RAC-PK, a pleckstrin homology domain containing ser/thr kinase. EMBO J. 14, 4288–4295.PubMedGoogle Scholar
  28. 28.
    Andjelkovic, M., Jakubowicz, T., Cron, P., Ming. X.-F., Han, J.-W., and Hemmings, B. A. (1996) Activation and phosphorylation of a PH domain containig protein Kinase (RAC-PK/PKB) by serum and protein phosphatase Inhibitors. Proc. Natl. Acad. Sci. USA 93, 5699–5704.PubMedCrossRefGoogle Scholar
  29. 29.
    McCollam, L., Bonfini, L., Karlovich, C. A., Conway, B. R., Kozma, L. M., Banerjee, U., and Czech, M. P. (1995) Functional roles for the pleckstrin and Dbl homology regions in the Ras exchange factor Son-of-sevenless. J. Biol. Chem. 270, 15,954–15,957.PubMedCrossRefGoogle Scholar
  30. 30.
    Tsukada, S., Simon, M. I., Witte, O. N., and Katz, A. (1994) Binding of βγ-subunits of heterotrimeric G proteins to the PH domain of Bruton tyrosine kinase. Proc. Natl. Acad. Sci. USA 91, 11,256–11,260.PubMedCrossRefGoogle Scholar
  31. 31.
    Langhans-Rajasekaran, S. A., Wan, Y., and Huang, X.-Y. (1995) Activation of Tsk and Btk tyrosine kinases by G protein βγ-subunits. Proc. Natl. Acad. Sci. USA 92, 8601–8605.PubMedCrossRefGoogle Scholar
  32. 32.
    Koch, W. J., Inglese, J., Stone, W. C., and Lefkowitz, R. J. (1993) The binding site for the βγ-subunits of heterotrimeric G proteins on the β-adrenergic receptor kinase. J. Biol. Chem. 268, 8256–8260.PubMedGoogle Scholar
  33. 33.
    Touhara, K., Inglese, J., Pitscher, J. A., Shaw, G., and Lefkowitz, R. J. (1994) Binding of βγ-subunits to pleckstrin homology domains. J. Biol. Chem. 269, 10,217–10,220.PubMedGoogle Scholar
  34. 34.
    Rebecchi, M., Peterson, A., and McLaughlin, S. (1992) Phosphoinositide-specific phospholipase C-d1 binds with high affinity to phospholipid vesicles containing phosphatidylinositol 4,5-bisphosphate. Biochemistry 31, 12,742–12,747.PubMedCrossRefGoogle Scholar
  35. 35.
    Garcia, P., Gupta, R., Shah, S., Morris, A. J., Rudge, S. A., Scarlata, S., Petrova, V. McLaughlin, S., and Rebecchi, M. (1995) The pleckstrin homology domain of Phospholipase c-δ1 binds with high affinity to phosphatidylinositol 4,5-bisphosphate in bilayer membranes. Biochemistry 34, 16,228–16,234.PubMedCrossRefGoogle Scholar
  36. 36.
    Harlan, J. E., Hajduk, P. J., Yoon, H. S., and Fesik, S. W. (1994) Pleckstrin homology domains bind to phosphatidylinositol-4,5-bisphosphate. Nature 371, 168–170.PubMedCrossRefGoogle Scholar
  37. 37.
    Lemmon, M. A., Ferguson, K. M., O’Brien, R., Sigler, P. B., and Schlessinger, J. (1995) Specific and high-affinity binding of inositol phosphates to an isolated pleckstrin homology domain. Proc. Natl. Acad. Sci. USA 92, 10,472–10,476.PubMedCrossRefGoogle Scholar
  38. 38.
    Zheng, J., Cahill, S., Lemmon, M. A., Fushman, D., Schlessinger, J., and Cowburn, D. (1996) Identification of the binding site for acidic phospholipids on the PH domain of dynamin: implications for stimulation of GTPase activity. J. Mol. Biol. 255, 14–21.PubMedCrossRefGoogle Scholar
  39. 39.
    Reddy, K. K., Saady, M., Whited, G., and Falck, J. R. (1995) Intracellular mediators: synthesis of L-α-phosphatidyl-D-myo-inositol 3,4,5-trisphosphate and glyceryl ether analogs. J. Org. Chem. 60, 3385–3390.CrossRefGoogle Scholar
  40. 40.
    Fech, M., Andjelkovic, M., Ingley, E., Reddy, K. K., Falck, J. R., and Hemmings, B. A. (1997) High affinity binding of inositol phosphates and phosphoinositides to the pleckstrin homology domain of RAC/protein kinase B and their influence on kinase activity. J. Biol. Chem. 272, 8474–8481.CrossRefGoogle Scholar

Copyright information

© Humana Press Inc. 1998

Authors and Affiliations

  • Matthias Frech
    • 1
  • Brian A. Hemmings
    • 1
  1. 1.Friedrich Miescher InstituteBaselSwitzerland

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