Identification and analysis of PH domain-containing targets of phosphatidylinositol 3-kinase using a novel in vivo assay in yeast (original) (raw)

Abstract

Phosphatidylinositol 3-kinase (PI3K) mediates a variety of cellular responses by generating PtdIns(3,4)P2 and PtdIns(3,4,5)P3. These 3-phosphoinositides then function directly as second messengers to activate downstream signaling molecules by binding pleckstrin homology (PH) domains in these signaling molecules. We have established a novel assay in the yeast Saccharomyces cerevisiae to identify proteins that bind PtdIns(3,4)P2 and PtdIns(3,4,5)P3 in vivo which we have called TOPIS (Targets of PI3K Identification System). The assay uses a plasma membrane-targeted Ras to complement a temperature-sensitive CDC25 Ras exchange factor in yeast. Coexpression of PI3K and a fusion protein of activated Ras joined to a PH domain known to bind PtdIns(3,4)P2 (AKT) or PtdIns(3,4,5)P3 (BTK) rescues yeast growth at the non-permissive temperature of 37 degreesC. Using this assay, we have identified several amino acids in the beta1-beta2 region of PH domains that are critical for high affinity binding to PtdIns(3,4)P2 and/or PtdIns(3,4,5)P3, and we have proposed a structural model for how these PH domains might bind PI3K products with high affinity. From these data, we derived a consensus sequence which predicts high-affinity binding to PtdIns(3, 4)P2 and/or PtdIns(3,4,5)P3, and we have identified several new PH domain-containing proteins that bind PI3K products, including Gab1, Dos, myosinX, and Sbf1. Use of this assay to screen for novel cDNAs which rescue yeast at the non-permissive temperature should provide a powerful approach for uncovering additional targets of PI3K.

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Selected References

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  1. Abagyan R. A., Batalov S. Do aligned sequences share the same fold? J Mol Biol. 1997 Oct 17;273(1):355–368. doi: 10.1006/jmbi.1997.1287. [DOI] [PubMed] [Google Scholar]
  2. Alessi D. R., Deak M., Casamayor A., Caudwell F. B., Morrice N., Norman D. G., Gaffney P., Reese C. B., MacDougall C. N., Harbison D. 3-Phosphoinositide-dependent protein kinase-1 (PDK1): structural and functional homology with the Drosophila DSTPK61 kinase. Curr Biol. 1997 Oct 1;7(10):776–789. doi: 10.1016/s0960-9822(06)00336-8. [DOI] [PubMed] [Google Scholar]
  3. Aronheim A., Engelberg D., Li N., al-Alawi N., Schlessinger J., Karin M. Membrane targeting of the nucleotide exchange factor Sos is sufficient for activating the Ras signaling pathway. Cell. 1994 Sep 23;78(6):949–961. doi: 10.1016/0092-8674(94)90271-2. [DOI] [PubMed] [Google Scholar]
  4. Aronheim A. Improved efficiency sos recruitment system: expression of the mammalian GAP reduces isolation of Ras GTPase false positives. Nucleic Acids Res. 1997 Aug 15;25(16):3373–3374. doi: 10.1093/nar/25.16.3373. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Aronheim A., Zandi E., Hennemann H., Elledge S. J., Karin M. Isolation of an AP-1 repressor by a novel method for detecting protein-protein interactions. Mol Cell Biol. 1997 Jun;17(6):3094–3102. doi: 10.1128/mcb.17.6.3094. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. August A., Sadra A., Dupont B., Hanafusa H. Src-induced activation of inducible T cell kinase (ITK) requires phosphatidylinositol 3-kinase activity and the Pleckstrin homology domain of inducible T cell kinase. Proc Natl Acad Sci U S A. 1997 Oct 14;94(21):11227–11232. doi: 10.1073/pnas.94.21.11227. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Bae Y. S., Cantley L. G., Chen C. S., Kim S. R., Kwon K. S., Rhee S. G. Activation of phospholipase C-gamma by phosphatidylinositol 3,4,5-trisphosphate. J Biol Chem. 1998 Feb 20;273(8):4465–4469. doi: 10.1074/jbc.273.8.4465. [DOI] [PubMed] [Google Scholar]
  8. Bairoch A., Bucher P., Hofmann K. The PROSITE database, its status in 1997. Nucleic Acids Res. 1997 Jan 1;25(1):217–221. doi: 10.1093/nar/25.1.217. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Barylko B., Binns D., Lin K. M., Atkinson M. A., Jameson D. M., Yin H. L., Albanesi J. P. Synergistic activation of dynamin GTPase by Grb2 and phosphoinositides. J Biol Chem. 1998 Feb 6;273(6):3791–3797. doi: 10.1074/jbc.273.6.3791. [DOI] [PubMed] [Google Scholar]
  10. Burgering B. M., Coffer P. J. Protein kinase B (c-Akt) in phosphatidylinositol-3-OH kinase signal transduction. Nature. 1995 Aug 17;376(6541):599–602. doi: 10.1038/376599a0. [DOI] [PubMed] [Google Scholar]
  11. Cardozo T., Totrov M., Abagyan R. Homology modeling by the ICM method. Proteins. 1995 Nov;23(3):403–414. doi: 10.1002/prot.340230314. [DOI] [PubMed] [Google Scholar]
  12. Carpenter C. L., Cantley L. C. Phosphoinositide kinases. Biochemistry. 1990 Dec 25;29(51):11147–11156. doi: 10.1021/bi00503a001. [DOI] [PubMed] [Google Scholar]
  13. Carpenter C. L., Cantley L. C. Phosphoinositide kinases. Curr Opin Cell Biol. 1996 Apr;8(2):153–158. doi: 10.1016/s0955-0674(96)80060-3. [DOI] [PubMed] [Google Scholar]
  14. Chen R. H., Corbalan-Garcia S., Bar-Sagi D. The role of the PH domain in the signal-dependent membrane targeting of Sos. EMBO J. 1997 Mar 17;16(6):1351–1359. doi: 10.1093/emboj/16.6.1351. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Colicelli J., Birchmeier C., Michaeli T., O'Neill K., Riggs M., Wigler M. Isolation and characterization of a mammalian gene encoding a high-affinity cAMP phosphodiesterase. Proc Natl Acad Sci U S A. 1989 May;86(10):3599–3603. doi: 10.1073/pnas.86.10.3599. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Cui X., De Vivo I., Slany R., Miyamoto A., Firestein R., Cleary M. L. Association of SET domain and myotubularin-related proteins modulates growth control. Nat Genet. 1998 Apr;18(4):331–337. doi: 10.1038/ng0498-331. [DOI] [PubMed] [Google Scholar]
  17. De Camilli P., Emr S. D., McPherson P. S., Novick P. Phosphoinositides as regulators in membrane traffic. Science. 1996 Mar 15;271(5255):1533–1539. doi: 10.1126/science.271.5255.1533. [DOI] [PubMed] [Google Scholar]
  18. Downward J. Lipid-regulated kinases: some common themes at last. Science. 1998 Jan 30;279(5351):673–674. doi: 10.1126/science.279.5351.673. [DOI] [PubMed] [Google Scholar]
  19. Dudek H., Datta S. R., Franke T. F., Birnbaum M. J., Yao R., Cooper G. M., Segal R. A., Kaplan D. R., Greenberg M. E. Regulation of neuronal survival by the serine-threonine protein kinase Akt. Science. 1997 Jan 31;275(5300):661–665. doi: 10.1126/science.275.5300.661. [DOI] [PubMed] [Google Scholar]
  20. Escobedo J. A., Navankasattusas S., Kavanaugh W. M., Milfay D., Fried V. A., Williams L. T. cDNA cloning of a novel 85 kd protein that has SH2 domains and regulates binding of PI3-kinase to the PDGF beta-receptor. Cell. 1991 Apr 5;65(1):75–82. doi: 10.1016/0092-8674(91)90409-r. [DOI] [PubMed] [Google Scholar]
  21. Falasca M., Logan S. K., Lehto V. P., Baccante G., Lemmon M. A., Schlessinger J. Activation of phospholipase C gamma by PI 3-kinase-induced PH domain-mediated membrane targeting. EMBO J. 1998 Jan 15;17(2):414–422. doi: 10.1093/emboj/17.2.414. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Ferguson K. M., Lemmon M. A., Schlessinger J., Sigler P. B. Structure of the high affinity complex of inositol trisphosphate with a phospholipase C pleckstrin homology domain. Cell. 1995 Dec 15;83(6):1037–1046. doi: 10.1016/0092-8674(95)90219-8. [DOI] [PubMed] [Google Scholar]
  23. Franke T. F., Kaplan D. R., Cantley L. C. PI3K: downstream AKTion blocks apoptosis. Cell. 1997 Feb 21;88(4):435–437. doi: 10.1016/s0092-8674(00)81883-8. [DOI] [PubMed] [Google Scholar]
  24. Franke T. F., Kaplan D. R., Cantley L. C., Toker A. Direct regulation of the Akt proto-oncogene product by phosphatidylinositol-3,4-bisphosphate. Science. 1997 Jan 31;275(5300):665–668. doi: 10.1126/science.275.5300.665. [DOI] [PubMed] [Google Scholar]
  25. Franke T. F., Yang S. I., Chan T. O., Datta K., Kazlauskas A., Morrison D. K., Kaplan D. R., Tsichlis P. N. The protein kinase encoded by the Akt proto-oncogene is a target of the PDGF-activated phosphatidylinositol 3-kinase. Cell. 1995 Jun 2;81(5):727–736. doi: 10.1016/0092-8674(95)90534-0. [DOI] [PubMed] [Google Scholar]
  26. Frech M., Andjelkovic M., Ingley E., Reddy K. K., Falck J. R., Hemmings B. A. 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. 1997 Mar 28;272(13):8474–8481. doi: 10.1074/jbc.272.13.8474. [DOI] [PubMed] [Google Scholar]
  27. Fukuda M., Kojima T., Kabayama H., Mikoshiba K. Mutation of the pleckstrin homology domain of Bruton's tyrosine kinase in immunodeficiency impaired inositol 1,3,4,5-tetrakisphosphate binding capacity. J Biol Chem. 1996 Nov 29;271(48):30303–30306. doi: 10.1074/jbc.271.48.30303. [DOI] [PubMed] [Google Scholar]
  28. Fukuda M., Mikoshiba K. Structure-function relationships of the mouse Gap1m. Determination of the inositol 1,3,4,5-tetrakisphosphate-binding domain. J Biol Chem. 1996 Aug 2;271(31):18838–18842. doi: 10.1074/jbc.271.31.18838. [DOI] [PubMed] [Google Scholar]
  29. Fukuda M., Mikoshiba K. The function of inositol high polyphosphate binding proteins. Bioessays. 1997 Jul;19(7):593–603. doi: 10.1002/bies.950190710. [DOI] [PubMed] [Google Scholar]
  30. Gibson T. J., Hyvönen M., Musacchio A., Saraste M., Birney E. PH domain: the first anniversary. Trends Biochem Sci. 1994 Sep;19(9):349–353. doi: 10.1016/0968-0004(94)90108-2. [DOI] [PubMed] [Google Scholar]
  31. Hammonds-Odie L. P., Jackson T. R., Profit A. A., Blader I. J., Turck C. W., Prestwich G. D., Theibert A. B. Identification and cloning of centaurin-alpha. A novel phosphatidylinositol 3,4,5-trisphosphate-binding protein from rat brain. J Biol Chem. 1996 Aug 2;271(31):18859–18868. doi: 10.1074/jbc.271.31.18859. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Han J., Luby-Phelps K., Das B., Shu X., Xia Y., Mosteller R. D., Krishna U. M., Falck J. R., White M. A., Broek D. Role of substrates and products of PI 3-kinase in regulating activation of Rac-related guanosine triphosphatases by Vav. Science. 1998 Jan 23;279(5350):558–560. doi: 10.1126/science.279.5350.558. [DOI] [PubMed] [Google Scholar]
  33. Harlan J. E., Hajduk P. J., Yoon H. S., Fesik S. W. Pleckstrin homology domains bind to phosphatidylinositol-4,5-bisphosphate. Nature. 1994 Sep 8;371(6493):168–170. doi: 10.1038/371168a0. [DOI] [PubMed] [Google Scholar]
  34. Harlan J. E., Yoon H. S., Hajduk P. J., Fesik S. W. Structural characterization of the interaction between a pleckstrin homology domain and phosphatidylinositol 4,5-bisphosphate. Biochemistry. 1995 Aug 8;34(31):9859–9864. doi: 10.1021/bi00031a006. [DOI] [PubMed] [Google Scholar]
  35. Herbst R., Carroll P. M., Allard J. D., Schilling J., Raabe T., Simon M. A. Daughter of sevenless is a substrate of the phosphotyrosine phosphatase Corkscrew and functions during sevenless signaling. Cell. 1996 Jun 14;85(6):899–909. doi: 10.1016/s0092-8674(00)81273-8. [DOI] [PubMed] [Google Scholar]
  36. Hiles I. D., Otsu M., Volinia S., Fry M. J., Gout I., Dhand R., Panayotou G., Ruiz-Larrea F., Thompson A., Totty N. F. Phosphatidylinositol 3-kinase: structure and expression of the 110 kd catalytic subunit. Cell. 1992 Aug 7;70(3):419–429. doi: 10.1016/0092-8674(92)90166-a. [DOI] [PubMed] [Google Scholar]
  37. Holgado-Madruga M., Emlet D. R., Moscatello D. K., Godwin A. K., Wong A. J. A Grb2-associated docking protein in EGF- and insulin-receptor signalling. Nature. 1996 Feb 8;379(6565):560–564. doi: 10.1038/379560a0. [DOI] [PubMed] [Google Scholar]
  38. Hu P., Mondino A., Skolnik E. Y., Schlessinger J. Cloning of a novel, ubiquitously expressed human phosphatidylinositol 3-kinase and identification of its binding site on p85. Mol Cell Biol. 1993 Dec;13(12):7677–7688. doi: 10.1128/mcb.13.12.7677. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Hu P., Schlessinger J. Direct association of p110 beta phosphatidylinositol 3-kinase with p85 is mediated by an N-terminal fragment of p110 beta. Mol Cell Biol. 1994 Apr;14(4):2577–2583. doi: 10.1128/mcb.14.4.2577. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Hyvönen M., Macias M. J., Nilges M., Oschkinat H., Saraste M., Wilmanns M. Structure of the binding site for inositol phosphates in a PH domain. EMBO J. 1995 Oct 2;14(19):4676–4685. doi: 10.1002/j.1460-2075.1995.tb00149.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Hyvönen M., Saraste M. Structure of the PH domain and Btk motif from Bruton's tyrosine kinase: molecular explanations for X-linked agammaglobulinaemia. EMBO J. 1997 Jun 16;16(12):3396–3404. doi: 10.1093/emboj/16.12.3396. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Irvine R., Cullen P. Inositol phosphates - whither bound? Intracellular signalling. Curr Biol. 1996 May 1;6(5):537–540. doi: 10.1016/s0960-9822(02)00536-5. [DOI] [PubMed] [Google Scholar]
  43. Isakoff S. J., Yu Y. P., Su Y. C., Blaikie P., Yajnik V., Rose E., Weidner K. M., Sachs M., Margolis B., Skolnik E. Y. Interaction between the phosphotyrosine binding domain of Shc and the insulin receptor is required for Shc phosphorylation by insulin in vivo. J Biol Chem. 1996 Feb 23;271(8):3959–3962. doi: 10.1074/jbc.271.8.3959. [DOI] [PubMed] [Google Scholar]
  44. James S. R., Downes C. P., Gigg R., Grove S. J., Holmes A. B., Alessi D. R. Specific binding of the Akt-1 protein kinase to phosphatidylinositol 3,4,5-trisphosphate without subsequent activation. Biochem J. 1996 May 1;315(Pt 3):709–713. doi: 10.1042/bj3150709. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Karlin S., Altschul S. F. Methods for assessing the statistical significance of molecular sequence features by using general scoring schemes. Proc Natl Acad Sci U S A. 1990 Mar;87(6):2264–2268. doi: 10.1073/pnas.87.6.2264. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Klarlund J. K., Guilherme A., Holik J. J., Virbasius J. V., Chawla A., Czech M. P. Signaling by phosphoinositide-3,4,5-trisphosphate through proteins containing pleckstrin and Sec7 homology domains. Science. 1997 Mar 28;275(5308):1927–1930. doi: 10.1126/science.275.5308.1927. [DOI] [PubMed] [Google Scholar]
  47. Klarlund J. K., Rameh L. E., Cantley L. C., Buxton J. M., Holik J. J., Sakelis C., Patki V., Corvera S., Czech M. P. Regulation of GRP1-catalyzed ADP ribosylation factor guanine nucleotide exchange by phosphatidylinositol 3,4,5-trisphosphate. J Biol Chem. 1998 Jan 23;273(4):1859–1862. doi: 10.1074/jbc.273.4.1859. [DOI] [PubMed] [Google Scholar]
  48. Klippel A., Escobedo J. A., Hu Q., Williams L. T. A region of the 85-kilodalton (kDa) subunit of phosphatidylinositol 3-kinase binds the 110-kDa catalytic subunit in vivo. Mol Cell Biol. 1993 Sep;13(9):5560–5566. doi: 10.1128/mcb.13.9.5560. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Klippel A., Kavanaugh W. M., Pot D., Williams L. T. A specific product of phosphatidylinositol 3-kinase directly activates the protein kinase Akt through its pleckstrin homology domain. Mol Cell Biol. 1997 Jan;17(1):338–344. doi: 10.1128/mcb.17.1.338. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Kodaki T., Woscholski R., Emr S., Waterfield M. D., Nurse P., Parker P. J. Mammalian phosphatidylinositol 3'-kinase induces a lethal phenotype on expression in Schizosaccharomyces pombe; comparison with the VPS34 gene product. Eur J Biochem. 1994 Feb 1;219(3):775–780. doi: 10.1111/j.1432-1033.1994.tb18557.x. [DOI] [PubMed] [Google Scholar]
  51. Kodaki T., Woscholski R., Hallberg B., Rodriguez-Viciana P., Downward J., Parker P. J. The activation of phosphatidylinositol 3-kinase by Ras. Curr Biol. 1994 Sep 1;4(9):798–806. doi: 10.1016/s0960-9822(00)00177-9. [DOI] [PubMed] [Google Scholar]
  52. Kojima T., Fukuda M., Watanabe Y., Hamazato F., Mikoshiba K. Characterization of the pleckstrin homology domain of Btk as an inositol polyphosphate and phosphoinositide binding domain. Biochem Biophys Res Commun. 1997 Jul 18;236(2):333–339. doi: 10.1006/bbrc.1997.6947. [DOI] [PubMed] [Google Scholar]
  53. Koshiba S., Kigawa T., Kim J. H., Shirouzu M., Bowtell D., Yokoyama S. The solution structure of the pleckstrin homology domain of mouse Son-of-sevenless 1 (mSos1). J Mol Biol. 1997 Jun 20;269(4):579–591. doi: 10.1006/jmbi.1997.1041. [DOI] [PubMed] [Google Scholar]
  54. Kubiseski T. J., Chook Y. M., Parris W. E., Rozakis-Adcock M., Pawson T. High affinity binding of the pleckstrin homology domain of mSos1 to phosphatidylinositol (4,5)-bisphosphate. J Biol Chem. 1997 Jan 17;272(3):1799–1804. doi: 10.1074/jbc.272.3.1799. [DOI] [PubMed] [Google Scholar]
  55. Lemmon M. A., Ferguson K. M., O'Brien R., Sigler P. B., Schlessinger J. Specific and high-affinity binding of inositol phosphates to an isolated pleckstrin homology domain. Proc Natl Acad Sci U S A. 1995 Nov 7;92(23):10472–10476. doi: 10.1073/pnas.92.23.10472. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Lemmon M. A., Ferguson K. M., Schlessinger J. PH domains: diverse sequences with a common fold recruit signaling molecules to the cell surface. Cell. 1996 May 31;85(5):621–624. doi: 10.1016/s0092-8674(00)81022-3. [DOI] [PubMed] [Google Scholar]
  57. Lockyer P. J., Bottomley J. R., Reynolds J. S., McNulty T. J., Venkateswarlu K., Potter B. V., Dempsey C. E., Cullen P. J. Distinct subcellular localisations of the putative inositol 1,3,4,5-tetrakisphosphate receptors GAP1IP4BP and GAP1m result from the GAP1IP4BP PH domain directing plasma membrane targeting. Curr Biol. 1997 Dec 1;7(12):1007–1010. doi: 10.1016/s0960-9822(06)00423-4. [DOI] [PubMed] [Google Scholar]
  58. Logan S. K., Falasca M., Hu P., Schlessinger J. Phosphatidylinositol 3-kinase mediates epidermal growth factor-induced activation of the c-Jun N-terminal kinase signaling pathway. Mol Cell Biol. 1997 Oct;17(10):5784–5790. doi: 10.1128/mcb.17.10.5784. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. M A L., M F., J S., K F. Regulatory recruitment of signalling molecules to the cell membrane by pleckstrinhomology domains. Trends Cell Biol. 1997 Jun;7(6):237–242. doi: 10.1016/S0962-8924(97)01065-9. [DOI] [PubMed] [Google Scholar]
  60. Mattsson P. T., Vihinen M., Smith C. I. X-linked agammaglobulinemia (XLA): a genetic tyrosine kinase (Btk) disease. Bioessays. 1996 Oct;18(10):825–834. doi: 10.1002/bies.950181009. [DOI] [PubMed] [Google Scholar]
  61. Mayer B. J., Ren R., Clark K. L., Baltimore D. A putative modular domain present in diverse signaling proteins. Cell. 1993 May 21;73(4):629–630. doi: 10.1016/0092-8674(93)90244-k. [DOI] [PubMed] [Google Scholar]
  62. Mermall V., Post P. L., Mooseker M. S. Unconventional myosins in cell movement, membrane traffic, and signal transduction. Science. 1998 Jan 23;279(5350):527–533. doi: 10.1126/science.279.5350.527. [DOI] [PubMed] [Google Scholar]
  63. Musacchio A., Gibson T., Rice P., Thompson J., Saraste M. The PH domain: a common piece in the structural patchwork of signalling proteins. Trends Biochem Sci. 1993 Sep;18(9):343–348. doi: 10.1016/0968-0004(93)90071-t. [DOI] [PubMed] [Google Scholar]
  64. Nimnual A. S., Yatsula B. A., Bar-Sagi D. Coupling of Ras and Rac guanosine triphosphatases through the Ras exchanger Sos. Science. 1998 Jan 23;279(5350):560–563. doi: 10.1126/science.279.5350.560. [DOI] [PubMed] [Google Scholar]
  65. Otsu M., Hiles I., Gout I., Fry M. J., Ruiz-Larrea F., Panayotou G., Thompson A., Dhand R., Hsuan J., Totty N. Characterization of two 85 kd proteins that associate with receptor tyrosine kinases, middle-T/pp60c-src complexes, and PI3-kinase. Cell. 1991 Apr 5;65(1):91–104. doi: 10.1016/0092-8674(91)90411-q. [DOI] [PubMed] [Google Scholar]
  66. Pitcher J. A., Touhara K., Payne E. S., Lefkowitz R. J. Pleckstrin homology domain-mediated membrane association and activation of the beta-adrenergic receptor kinase requires coordinate interaction with G beta gamma subunits and lipid. J Biol Chem. 1995 May 19;270(20):11707–11710. doi: 10.1074/jbc.270.20.11707. [DOI] [PubMed] [Google Scholar]
  67. Raabe T., Riesgo-Escovar J., Liu X., Bausenwein B. S., Deak P., Maröy P., Hafen E. DOS, a novel pleckstrin homology domain-containing protein required for signal transduction between sevenless and Ras1 in Drosophila. Cell. 1996 Jun 14;85(6):911–920. doi: 10.1016/s0092-8674(00)81274-x. [DOI] [PubMed] [Google Scholar]
  68. Rameh L. E., Arvidsson A. k., Carraway K. L., 3rd, Couvillon A. D., Rathbun G., Crompton A., VanRenterghem B., Czech M. P., Ravichandran K. S., Burakoff S. J. A comparative analysis of the phosphoinositide binding specificity of pleckstrin homology domains. J Biol Chem. 1997 Aug 29;272(35):22059–22066. doi: 10.1074/jbc.272.35.22059. [DOI] [PubMed] [Google Scholar]
  69. Rameh L. E., Chen C. S., Cantley L. C. Phosphatidylinositol (3,4,5)P3 interacts with SH2 domains and modulates PI 3-kinase association with tyrosine-phosphorylated proteins. Cell. 1995 Dec 1;83(5):821–830. doi: 10.1016/0092-8674(95)90195-7. [DOI] [PubMed] [Google Scholar]
  70. 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. Mutation of unique region of Bruton's tyrosine kinase in immunodeficient XID mice. Science. 1993 Jul 16;261(5119):358–361. doi: 10.1126/science.8332901. [DOI] [PubMed] [Google Scholar]
  71. Salim K., Bottomley M. J., Querfurth E., Zvelebil M. J., Gout I., Scaife R., Margolis R. L., Gigg R., Smith C. I., Driscoll P. C. Distinct specificity in the recognition of phosphoinositides by the pleckstrin homology domains of dynamin and Bruton's tyrosine kinase. EMBO J. 1996 Nov 15;15(22):6241–6250. [PMC free article] [PubMed] [Google Scholar]
  72. Scharenberg A. M., El-Hillal O., Fruman D. A., Beitz L. O., Li Z., Lin S., Gout I., Cantley L. C., Rawlings D. J., Kinet J. P. Phosphatidylinositol-3,4,5-trisphosphate (PtdIns-3,4,5-P3)/Tec kinase-dependent calcium signaling pathway: a target for SHIP-mediated inhibitory signals. EMBO J. 1998 Apr 1;17(7):1961–1972. doi: 10.1093/emboj/17.7.1961. [DOI] [PMC free article] [PubMed] [Google Scholar]
  73. Shaw G. The pleckstrin homology domain: an intriguing multifunctional protein module. Bioessays. 1996 Jan;18(1):35–46. doi: 10.1002/bies.950180109. [DOI] [PubMed] [Google Scholar]
  74. Skolnik E. Y., Batzer A., Li N., Lee C. H., Lowenstein E., Mohammadi M., Margolis B., Schlessinger J. The function of GRB2 in linking the insulin receptor to Ras signaling pathways. Science. 1993 Jun 25;260(5116):1953–1955. doi: 10.1126/science.8316835. [DOI] [PubMed] [Google Scholar]
  75. Stephens L. R., Eguinoa A., Erdjument-Bromage H., Lui M., Cooke F., Coadwell J., Smrcka A. S., Thelen M., Cadwallader K., Tempst P. The G beta gamma sensitivity of a PI3K is dependent upon a tightly associated adaptor, p101. Cell. 1997 Apr 4;89(1):105–114. doi: 10.1016/s0092-8674(00)80187-7. [DOI] [PubMed] [Google Scholar]
  76. Stephens L. R., Jackson T. R., Hawkins P. T. Agonist-stimulated synthesis of phosphatidylinositol(3,4,5)-trisphosphate: a new intracellular signalling system? Biochim Biophys Acta. 1993 Oct 7;1179(1):27–75. doi: 10.1016/0167-4889(93)90072-w. [DOI] [PubMed] [Google Scholar]
  77. Stephens L., Anderson K., Stokoe D., Erdjument-Bromage H., Painter G. F., Holmes A. B., Gaffney P. R., Reese C. B., McCormick F., Tempst P. Protein kinase B kinases that mediate phosphatidylinositol 3,4,5-trisphosphate-dependent activation of protein kinase B. Science. 1998 Jan 30;279(5351):710–714. doi: 10.1126/science.279.5351.710. [DOI] [PubMed] [Google Scholar]
  78. Stoyanov B., Volinia S., Hanck T., Rubio I., Loubtchenkov M., Malek D., Stoyanova S., Vanhaesebroeck B., Dhand R., Nürnberg B. Cloning and characterization of a G protein-activated human phosphoinositide-3 kinase. Science. 1995 Aug 4;269(5224):690–693. doi: 10.1126/science.7624799. [DOI] [PubMed] [Google Scholar]
  79. Superti-Furga G., Jönsson K., Courtneidge S. A. A functional screen in yeast for regulators and antagonizers of heterologous protein tyrosine kinases. Nat Biotechnol. 1996 May;14(5):600–605. doi: 10.1038/nbt0596-600. [DOI] [PubMed] [Google Scholar]
  80. Toker A., Cantley L. C. Signalling through the lipid products of phosphoinositide-3-OH kinase. Nature. 1997 Jun 12;387(6634):673–676. doi: 10.1038/42648. [DOI] [PubMed] [Google Scholar]
  81. Vanhaesebroeck B., Leevers S. J., Panayotou G., Waterfield M. D. Phosphoinositide 3-kinases: a conserved family of signal transducers. Trends Biochem Sci. 1997 Jul;22(7):267–272. doi: 10.1016/s0968-0004(97)01061-x. [DOI] [PubMed] [Google Scholar]
  82. Venkateswarlu K., Oatey P. B., Tavaré J. M., Cullen P. J. Insulin-dependent translocation of ARNO to the plasma membrane of adipocytes requires phosphatidylinositol 3-kinase. Curr Biol. 1998 Apr 9;8(8):463–466. doi: 10.1016/s0960-9822(98)70181-2. [DOI] [PubMed] [Google Scholar]
  83. Vihinen M., Iwata T., Kinnon C., Kwan S. P., Ochs H. D., Vorechovský I., Smith C. I. BTKbase, mutation database for X-linked agammaglobulinemia (XLA). Nucleic Acids Res. 1996 Jan 1;24(1):160–165. doi: 10.1093/nar/24.1.160. [DOI] [PMC free article] [PubMed] [Google Scholar]
  84. Vojtek A. B., Hollenberg S. M., Cooper J. A. Mammalian Ras interacts directly with the serine/threonine kinase Raf. Cell. 1993 Jul 16;74(1):205–214. doi: 10.1016/0092-8674(93)90307-c. [DOI] [PubMed] [Google Scholar]
  85. Weidner K. M., Di Cesare S., Sachs M., Brinkmann V., Behrens J., Birchmeier W. Interaction between Gab1 and the c-Met receptor tyrosine kinase is responsible for epithelial morphogenesis. Nature. 1996 Nov 14;384(6605):173–176. doi: 10.1038/384173a0. [DOI] [PubMed] [Google Scholar]
  86. Yang W., Desiderio S. BAP-135, a target for Bruton's tyrosine kinase in response to B cell receptor engagement. Proc Natl Acad Sci U S A. 1997 Jan 21;94(2):604–609. doi: 10.1073/pnas.94.2.604. [DOI] [PMC free article] [PubMed] [Google Scholar]
  87. Zheng J., Cahill S. M., Lemmon M. A., Fushman D., Schlessinger J., Cowburn D. Identification of the binding site for acidic phospholipids on the pH domain of dynamin: implications for stimulation of GTPase activity. J Mol Biol. 1996 Jan 12;255(1):14–21. doi: 10.1006/jmbi.1996.0002. [DOI] [PubMed] [Google Scholar]