The phosphotyrosine interaction domains of X11 and FE65 bind to distinct sites on the YENPTY motif of amyloid precursor protein (original) (raw)

Abstract

The phosphotyrosine interaction (PI) domains (also known as the PTB, or phosphotyrosine binding, domains) of Shc and IRS-1 are recently described domains that bind peptides phosphorylated on tyrosine residues. The PI/PTB domains differ from Src homology 2 (SH2) domains in that their binding specificity is determined by residues that lie amino terminal and not carboxy terminal to the phosphotyrosine. Recently, it has been appreciated that other cytoplasmic proteins also contain PI domains. We now show that the PI domain of X11 and one of the PI domains of FE65, two neuronal proteins, bind to the cytoplasmic domain of the amyloid precursor protein ((beta)APP). (beta)APP is an integral transmembrane glycoprotein whose cellular function is unknown. One of the processing pathways of (beta)APP leads to the secretion of A(beta), the major constituent of the amyloid deposited in the brain parenchyma and vessel walls of Alzheimer's disease patients. We have found that the X11 PI domain binds a YENPTY motif in the intracellular domain of (beta)APP that is strikingly similar to the NPXY motifs that bind the Shc and IRS-1 PI/PTB domains. However, unlike the case for binding of the Shc PI/PTB domain, tyrosine phosphorylation of the YENPTY motif is not required for the binding of (beta)APP to X11 or FE65. The binding site of the FE65 PI domain appears to be different from that of X11, as mutations within the YENPTY motif differentially affect the binding of X11 and FE65. Using site-directed mutagenesis, we have identified a crucial residue within the PI domain involved in X11 and FE65 binding to (beta)APP. The binding of X11 or FE65 PI domains to residues of the YENPTY motif of (beta)APP identifies PI domains as general protein interaction domains and may have important implications for the processing of (beta)APP.

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Selected References

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  1. Batzer A. G., Blaikie P., Nelson K., Schlessinger J., Margolis B. The phosphotyrosine interaction domain of Shc binds an LXNPXY motif on the epidermal growth factor receptor. Mol Cell Biol. 1995 Aug;15(8):4403–4409. doi: 10.1128/mcb.15.8.4403. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Batzer A. G., Rotin D., Ureña J. M., Skolnik E. Y., Schlessinger J. Hierarchy of binding sites for Grb2 and Shc on the epidermal growth factor receptor. Mol Cell Biol. 1994 Aug;14(8):5192–5201. doi: 10.1128/mcb.14.8.5192. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Blaikie P., Immanuel D., Wu J., Li N., Yajnik V., Margolis B. A region in Shc distinct from the SH2 domain can bind tyrosine-phosphorylated growth factor receptors. J Biol Chem. 1994 Dec 23;269(51):32031–32034. [PubMed] [Google Scholar]
  4. Bork P., Margolis B. A phosphotyrosine interaction domain. Cell. 1995 Mar 10;80(5):693–694. doi: 10.1016/0092-8674(95)90347-x. [DOI] [PubMed] [Google Scholar]
  5. Brenman J. E., Chao D. S., Gee S. H., McGee A. W., Craven S. E., Santillano D. R., Wu Z., Huang F., Xia H., Peters M. F. Interaction of nitric oxide synthase with the postsynaptic density protein PSD-95 and alpha1-syntrophin mediated by PDZ domains. Cell. 1996 Mar 8;84(5):757–767. doi: 10.1016/s0092-8674(00)81053-3. [DOI] [PubMed] [Google Scholar]
  6. Brenman J. E., Chao D. S., Xia H., Aldape K., Bredt D. S. Nitric oxide synthase complexed with dystrophin and absent from skeletal muscle sarcolemma in Duchenne muscular dystrophy. Cell. 1995 Sep 8;82(5):743–752. doi: 10.1016/0092-8674(95)90471-9. [DOI] [PubMed] [Google Scholar]
  7. Buxbaum J. D., Gandy S. E., Cicchetti P., Ehrlich M. E., Czernik A. J., Fracasso R. P., Ramabhadran T. V., Unterbeck A. J., Greengard P. Processing of Alzheimer beta/A4 amyloid precursor protein: modulation by agents that regulate protein phosphorylation. Proc Natl Acad Sci U S A. 1990 Aug;87(15):6003–6006. doi: 10.1073/pnas.87.15.6003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Charest A., Wagner J., Jacob S., McGlade C. J., Tremblay M. L. Phosphotyrosine-independent binding of SHC to the NPLH sequence of murine protein-tyrosine phosphatase-PEST. Evidence for extended phosphotyrosine binding/phosphotyrosine interaction domain recognition specificity. J Biol Chem. 1996 Apr 5;271(14):8424–8429. doi: 10.1074/jbc.271.14.8424. [DOI] [PubMed] [Google Scholar]
  9. Chen C., Okayama H. High-efficiency transformation of mammalian cells by plasmid DNA. Mol Cell Biol. 1987 Aug;7(8):2745–2752. doi: 10.1128/mcb.7.8.2745. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Chen H. I., Sudol M. The WW domain of Yes-associated protein binds a proline-rich ligand that differs from the consensus established for Src homology 3-binding modules. Proc Natl Acad Sci U S A. 1995 Aug 15;92(17):7819–7823. doi: 10.1073/pnas.92.17.7819. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Chen W. J., Goldstein J. L., Brown M. S. NPXY, a sequence often found in cytoplasmic tails, is required for coated pit-mediated internalization of the low density lipoprotein receptor. J Biol Chem. 1990 Feb 25;265(6):3116–3123. [PubMed] [Google Scholar]
  12. Chen Y., Grall D., Salcini A. E., Pelicci P. G., Pouysségur J., Van Obberghen-Schilling E. Shc adaptor proteins are key transducers of mitogenic signaling mediated by the G protein-coupled thrombin receptor. EMBO J. 1996 Mar 1;15(5):1037–1044. [PMC free article] [PubMed] [Google Scholar]
  13. Craparo A., O'Neill T. J., Gustafson T. A. Non-SH2 domains within insulin receptor substrate-1 and SHC mediate their phosphotyrosine-dependent interaction with the NPEY motif of the insulin-like growth factor I receptor. J Biol Chem. 1995 Jun 30;270(26):15639–15643. doi: 10.1074/jbc.270.26.15639. [DOI] [PubMed] [Google Scholar]
  14. Cutler R. L., Liu L., Damen J. E., Krystal G. Multiple cytokines induce the tyrosine phosphorylation of Shc and its association with Grb2 in hemopoietic cells. J Biol Chem. 1993 Oct 15;268(29):21463–21465. [PubMed] [Google Scholar]
  15. De Strooper B., Umans L., Van Leuven F., Van Den Berghe H. Study of the synthesis and secretion of normal and artificial mutants of murine amyloid precursor protein (APP): cleavage of APP occurs in a late compartment of the default secretion pathway. J Cell Biol. 1993 Apr;121(2):295–304. doi: 10.1083/jcb.121.2.295. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Dikic I., Batzer A. G., Blaikie P., Obermeier A., Ullrich A., Schlessinger J., Margolis B. Shc binding to nerve growth factor receptor is mediated by the phosphotyrosine interaction domain. J Biol Chem. 1995 Jun 23;270(25):15125–15129. doi: 10.1074/jbc.270.25.15125. [DOI] [PubMed] [Google Scholar]
  17. Doyle D. A., Lee A., Lewis J., Kim E., Sheng M., MacKinnon R. Crystal structures of a complexed and peptide-free membrane protein-binding domain: molecular basis of peptide recognition by PDZ. Cell. 1996 Jun 28;85(7):1067–1076. doi: 10.1016/s0092-8674(00)81307-0. [DOI] [PubMed] [Google Scholar]
  18. Duclos F., Boschert U., Sirugo G., Mandel J. L., Hen R., Koenig M. Gene in the region of the Friedreich ataxia locus encodes a putative transmembrane protein expressed in the nervous system. Proc Natl Acad Sci U S A. 1993 Jan 1;90(1):109–113. doi: 10.1073/pnas.90.1.109. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Duilio A., Zambrano N., Mogavero A. R., Ammendola R., Cimino F., Russo T. A rat brain mRNA encoding a transcriptional activator homologous to the DNA binding domain of retroviral integrases. Nucleic Acids Res. 1991 Oct 11;19(19):5269–5274. doi: 10.1093/nar/19.19.5269. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Fiore F., Zambrano N., Minopoli G., Donini V., Duilio A., Russo T. The regions of the Fe65 protein homologous to the phosphotyrosine interaction/phosphotyrosine binding domain of Shc bind the intracellular domain of the Alzheimer's amyloid precursor protein. J Biol Chem. 1995 Dec 29;270(52):30853–30856. doi: 10.1074/jbc.270.52.30853. [DOI] [PubMed] [Google Scholar]
  21. Glenner G. G., Wong C. W. Alzheimer's disease and Down's syndrome: sharing of a unique cerebrovascular amyloid fibril protein. Biochem Biophys Res Commun. 1984 Aug 16;122(3):1131–1135. doi: 10.1016/0006-291x(84)91209-9. [DOI] [PubMed] [Google Scholar]
  22. Guo M., Jan L. Y., Jan Y. N. Control of daughter cell fates during asymmetric division: interaction of Numb and Notch. Neuron. 1996 Jul;17(1):27–41. doi: 10.1016/s0896-6273(00)80278-0. [DOI] [PubMed] [Google Scholar]
  23. Gustafson T. A., He W., Craparo A., Schaub C. D., O'Neill T. J. Phosphotyrosine-dependent interaction of SHC and insulin receptor substrate 1 with the NPEY motif of the insulin receptor via a novel non-SH2 domain. Mol Cell Biol. 1995 May;15(5):2500–2508. doi: 10.1128/mcb.15.5.2500. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Haass C., Hung A. Y., Schlossmacher M. G., Teplow D. B., Selkoe D. J. beta-Amyloid peptide and a 3-kDa fragment are derived by distinct cellular mechanisms. J Biol Chem. 1993 Feb 15;268(5):3021–3024. [PubMed] [Google Scholar]
  25. He W., O'Neill T. J., Gustafson T. A. Distinct modes of interaction of SHC and insulin receptor substrate-1 with the insulin receptor NPEY region via non-SH2 domains. J Biol Chem. 1995 Oct 6;270(40):23258–23262. doi: 10.1074/jbc.270.40.23258. [DOI] [PubMed] [Google Scholar]
  26. 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]
  27. Kang J., Lemaire H. G., Unterbeck A., Salbaum J. M., Masters C. L., Grzeschik K. H., Multhaup G., Beyreuther K., Müller-Hill B. The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor. Nature. 1987 Feb 19;325(6106):733–736. doi: 10.1038/325733a0. [DOI] [PubMed] [Google Scholar]
  28. Kavanaugh W. M., Williams L. T. An alternative to SH2 domains for binding tyrosine-phosphorylated proteins. Science. 1994 Dec 16;266(5192):1862–1865. doi: 10.1126/science.7527937. [DOI] [PubMed] [Google Scholar]
  29. Koo E. H., Squazzo S. L. Evidence that production and release of amyloid beta-protein involves the endocytic pathway. J Biol Chem. 1994 Jul 1;269(26):17386–17389. [PubMed] [Google Scholar]
  30. Kornau H. C., Schenker L. T., Kennedy M. B., Seeburg P. H. Domain interaction between NMDA receptor subunits and the postsynaptic density protein PSD-95. Science. 1995 Sep 22;269(5231):1737–1740. doi: 10.1126/science.7569905. [DOI] [PubMed] [Google Scholar]
  31. Lai A., Sisodia S. S., Trowbridge I. S. Characterization of sorting signals in the beta-amyloid precursor protein cytoplasmic domain. J Biol Chem. 1995 Feb 24;270(8):3565–3573. [PubMed] [Google Scholar]
  32. Lev S., Moreno H., Martinez R., Canoll P., Peles E., Musacchio J. M., Plowman G. D., Rudy B., Schlessinger J. Protein tyrosine kinase PYK2 involved in Ca(2+)-induced regulation of ion channel and MAP kinase functions. Nature. 1995 Aug 31;376(6543):737–745. doi: 10.1038/376737a0. [DOI] [PubMed] [Google Scholar]
  33. Lowenstein E. J., Daly R. J., Batzer A. G., Li W., Margolis B., Lammers R., Ullrich A., Skolnik E. Y., Bar-Sagi D., Schlessinger J. The SH2 and SH3 domain-containing protein GRB2 links receptor tyrosine kinases to ras signaling. Cell. 1992 Aug 7;70(3):431–442. doi: 10.1016/0092-8674(92)90167-b. [DOI] [PubMed] [Google Scholar]
  34. Margolis B., Li N., Koch A., Mohammadi M., Hurwitz D. R., Zilberstein A., Ullrich A., Pawson T., Schlessinger J. The tyrosine phosphorylated carboxyterminus of the EGF receptor is a binding site for GAP and PLC-gamma. EMBO J. 1990 Dec;9(13):4375–4380. doi: 10.1002/j.1460-2075.1990.tb07887.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Margolis B., Rhee S. G., Felder S., Mervic M., Lyall R., Levitzki A., Ullrich A., Zilberstein A., Schlessinger J. EGF induces tyrosine phosphorylation of phospholipase C-II: a potential mechanism for EGF receptor signaling. Cell. 1989 Jun 30;57(7):1101–1107. doi: 10.1016/0092-8674(89)90047-0. [DOI] [PubMed] [Google Scholar]
  36. Margolis B., Silvennoinen O., Comoglio F., Roonprapunt C., Skolnik E., Ullrich A., Schlessinger J. High-efficiency expression/cloning of epidermal growth factor-receptor-binding proteins with Src homology 2 domains. Proc Natl Acad Sci U S A. 1992 Oct 1;89(19):8894–8898. doi: 10.1073/pnas.89.19.8894. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Masters C. L., Simms G., Weinman N. A., Multhaup G., McDonald B. L., Beyreuther K. Amyloid plaque core protein in Alzheimer disease and Down syndrome. Proc Natl Acad Sci U S A. 1985 Jun;82(12):4245–4249. doi: 10.1073/pnas.82.12.4245. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Nordstedt C., Caporaso G. L., Thyberg J., Gandy S. E., Greengard P. Identification of the Alzheimer beta/A4 amyloid precursor protein in clathrin-coated vesicles purified from PC12 cells. J Biol Chem. 1993 Jan 5;268(1):608–612. [PubMed] [Google Scholar]
  39. Ooi J., Yajnik V., Immanuel D., Gordon M., Moskow J. J., Buchberg A. M., Margolis B. The cloning of Grb10 reveals a new family of SH2 domain proteins. Oncogene. 1995 Apr 20;10(8):1621–1630. [PubMed] [Google Scholar]
  40. Pawson T. Protein modules and signalling networks. Nature. 1995 Feb 16;373(6515):573–580. doi: 10.1038/373573a0. [DOI] [PubMed] [Google Scholar]
  41. Pelicci G., Lanfrancone L., Grignani F., McGlade J., Cavallo F., Forni G., Nicoletti I., Grignani F., Pawson T., Pelicci P. G. A novel transforming protein (SHC) with an SH2 domain is implicated in mitogenic signal transduction. Cell. 1992 Jul 10;70(1):93–104. doi: 10.1016/0092-8674(92)90536-l. [DOI] [PubMed] [Google Scholar]
  42. Ron D., Dressler H. pGSTag--a versatile bacterial expression plasmid for enzymatic labeling of recombinant proteins. Biotechniques. 1992 Dec;13(6):866–869. [PubMed] [Google Scholar]
  43. Rozakis-Adcock M., McGlade J., Mbamalu G., Pelicci G., Daly R., Li W., Batzer A., Thomas S., Brugge J., Pelicci P. G. Association of the Shc and Grb2/Sem5 SH2-containing proteins is implicated in activation of the Ras pathway by tyrosine kinases. Nature. 1992 Dec 17;360(6405):689–692. doi: 10.1038/360689a0. [DOI] [PubMed] [Google Scholar]
  44. Sato T., Irie S., Kitada S., Reed J. C. FAP-1: a protein tyrosine phosphatase that associates with Fas. Science. 1995 Apr 21;268(5209):411–415. doi: 10.1126/science.7536343. [DOI] [PubMed] [Google Scholar]
  45. Schlessinger J. SH2/SH3 signaling proteins. Curr Opin Genet Dev. 1994 Feb;4(1):25–30. doi: 10.1016/0959-437x(94)90087-6. [DOI] [PubMed] [Google Scholar]
  46. Simeone A., Duilio A., Fiore F., Acampora D., De Felice C., Faraonio R., Paolocci F., Cimino F., Russo T. Expression of the neuron-specific FE65 gene marks the development of embryo ganglionic derivatives. Dev Neurosci. 1994;16(1-2):53–60. doi: 10.1159/000112088. [DOI] [PubMed] [Google Scholar]
  47. Skolnik E. Y., Margolis B., Mohammadi M., Lowenstein E., Fischer R., Drepps A., Ullrich A., Schlessinger J. Cloning of PI3 kinase-associated p85 utilizing a novel method for expression/cloning of target proteins for receptor tyrosine kinases. Cell. 1991 Apr 5;65(1):83–90. doi: 10.1016/0092-8674(91)90410-z. [DOI] [PubMed] [Google Scholar]
  48. Songyang Z., Shoelson S. E., McGlade J., Olivier P., Pawson T., Bustelo X. R., Barbacid M., Sabe H., Hanafusa H., Yi T. Specific motifs recognized by the SH2 domains of Csk, 3BP2, fps/fes, GRB-2, HCP, SHC, Syk, and Vav. Mol Cell Biol. 1994 Apr;14(4):2777–2785. doi: 10.1128/mcb.14.4.2777. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Staub O., Dho S., Henry P., Correa J., Ishikawa T., McGlade J., Rotin D. WW domains of Nedd4 bind to the proline-rich PY motifs in the epithelial Na+ channel deleted in Liddle's syndrome. EMBO J. 1996 May 15;15(10):2371–2380. [PMC free article] [PubMed] [Google Scholar]
  50. Sudol M., Bork P., Einbond A., Kastury K., Druck T., Negrini M., Huebner K., Lehman D. Characterization of the mammalian YAP (Yes-associated protein) gene and its role in defining a novel protein module, the WW domain. J Biol Chem. 1995 Jun 16;270(24):14733–14741. doi: 10.1074/jbc.270.24.14733. [DOI] [PubMed] [Google Scholar]
  51. Sudol M., Chen H. I., Bougeret C., Einbond A., Bork P. Characterization of a novel protein-binding module--the WW domain. FEBS Lett. 1995 Aug 1;369(1):67–71. doi: 10.1016/0014-5793(95)00550-s. [DOI] [PubMed] [Google Scholar]
  52. Tartare-Deckert S., Sawka-Verhelle D., Murdaca J., Van Obberghen E. Evidence for a differential interaction of SHC and the insulin receptor substrate-1 (IRS-1) with the insulin-like growth factor-I (IGF-I) receptor in the yeast two-hybrid system. J Biol Chem. 1995 Oct 6;270(40):23456–23460. doi: 10.1074/jbc.270.40.23456. [DOI] [PubMed] [Google Scholar]
  53. VanderKuur J., Allevato G., Billestrup N., Norstedt G., Carter-Su C. Growth hormone-promoted tyrosyl phosphorylation of SHC proteins and SHC association with Grb2. J Biol Chem. 1995 Mar 31;270(13):7587–7593. doi: 10.1074/jbc.270.13.7587. [DOI] [PubMed] [Google Scholar]
  54. Waksman G., Kominos D., Robertson S. C., Pant N., Baltimore D., Birge R. B., Cowburn D., Hanafusa H., Mayer B. J., Overduin M. Crystal structure of the phosphotyrosine recognition domain SH2 of v-src complexed with tyrosine-phosphorylated peptides. Nature. 1992 Aug 20;358(6388):646–653. doi: 10.1038/358646a0. [DOI] [PubMed] [Google Scholar]
  55. Wolf G., Trüb T., Ottinger E., Groninga L., Lynch A., White M. F., Miyazaki M., Lee J., Shoelson S. E. PTB domains of IRS-1 and Shc have distinct but overlapping binding specificities. J Biol Chem. 1995 Nov 17;270(46):27407–27410. doi: 10.1074/jbc.270.46.27407. [DOI] [PubMed] [Google Scholar]
  56. Yajnik V., Blaikie P., Bork P., Margolis B. Identification of residues within the SHC phosphotyrosine binding/phosphotyrosine interaction domain crucial for phosphopeptide interaction. J Biol Chem. 1996 Jan 26;271(4):1813–1816. doi: 10.1074/jbc.271.4.1813. [DOI] [PubMed] [Google Scholar]
  57. Zhou M. M., Ravichandran K. S., Olejniczak E. F., Petros A. M., Meadows R. P., Sattler M., Harlan J. E., Wade W. S., Burakoff S. J., Fesik S. W. Structure and ligand recognition of the phosphotyrosine binding domain of Shc. Nature. 1995 Dec 7;378(6557):584–592. doi: 10.1038/378584a0. [DOI] [PubMed] [Google Scholar]
  58. van der Geer P., Wiley S., Gish G. D., Lai V. K., Stephens R., White M. F., Kaplan D., Pawson T. Identification of residues that control specific binding of the Shc phosphotyrosine-binding domain to phosphotyrosine sites. Proc Natl Acad Sci U S A. 1996 Feb 6;93(3):963–968. doi: 10.1073/pnas.93.3.963. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. van der Geer P., Wiley S., Lai V. K., Olivier J. P., Gish G. D., Stephens R., Kaplan D., Shoelson S., Pawson T. A conserved amino-terminal Shc domain binds to phosphotyrosine motifs in activated receptors and phosphopeptides. Curr Biol. 1995 Apr 1;5(4):404–412. doi: 10.1016/s0960-9822(95)00081-9. [DOI] [PubMed] [Google Scholar]