DIP Database of Interacting Proteins 611 Young Drive East; Los Angeles CA 90095; USA http://dip.doe-mbi.ucla.edu/ dip@mbi.ucla.edu 611 Young Drive East; Los Angeles CA 90095; USA http://dip.doe-mbi.ucla.edu/ guo-2006-1 Abeta and tau form soluble complexes that may promote self aggregation of both into the insoluble forms observed in Alzheimer's disease. in vitro In vitro protein kinase assay protein kinase assay western blot western blot Immuno blot Immuno blot Guo JP., Arai T., Miklossy J., McGeer PL. Synapse - Interactions of proteins with an established role in the presynapse. Details of GSK alpha and APP peptides taken from manufacturers' websites mcgeerpl@interchange.ubc.ca Proc. Natl. Acad. Sci. U.S.A. (0027-8424) 2006 IMEx Neurodegeneration - Publications depicting interactions involved in neurodegenerative diseases. Parkinsons - Interactions investigated in the context of Parkinsons disease Apoptosis - Interactions involving proteins with a function related to apoptosis Alzheimers - Interactions investigated in the context of Alzheimers disease Only protein-protein interactions imex curation guo-2006-3 Abeta and tau form soluble complexes that may promote self aggregation of both into the insoluble forms observed in Alzheimer's disease. in vitro In vitro spr surface plasmon resonance Optical biosensor BIAcore(r) BIAcore(r) Optical biosensor spr predetermined predetermined participant predetermined Guo JP., Arai T., Miklossy J., McGeer PL. Synapse - Interactions of proteins with an established role in the presynapse. Details of GSK alpha and APP peptides taken from manufacturers' websites mcgeerpl@interchange.ubc.ca Proc. Natl. Acad. Sci. U.S.A. (0027-8424) 2006 IMEx Neurodegeneration - Publications depicting interactions involved in neurodegenerative diseases. Parkinsons - Interactions investigated in the context of Parkinsons disease Apoptosis - Interactions involving proteins with a function related to apoptosis Alzheimers - Interactions investigated in the context of Alzheimers disease Only protein-protein interactions imex curation guo-2006-2 Abeta and tau form soluble complexes that may promote self aggregation of both into the insoluble forms observed in Alzheimer's disease. in vitro In vitro peptide array peptide array western blot western blot Immuno blot Immuno blot Guo JP., Arai T., Miklossy J., McGeer PL. Synapse - Interactions of proteins with an established role in the presynapse. Details of GSK alpha and APP peptides taken from manufacturers' websites mcgeerpl@interchange.ubc.ca Proc. Natl. Acad. Sci. U.S.A. (0027-8424) 2006 IMEx Neurodegeneration - Publications depicting interactions involved in neurodegenerative diseases. Parkinsons - Interactions investigated in the context of Parkinsons disease Apoptosis - Interactions involving proteins with a function related to apoptosis Alzheimers - Interactions investigated in the context of Alzheimers disease Only protein-protein interactions imex curation guo-2006-4 Abeta and tau form soluble complexes that may promote self aggregation of both into the insoluble forms observed in Alzheimer's disease. in vitro In vitro elisa enzyme linked immunosorbent assay ELISA ELISA elisa antibody detection identification by antibody antibody detection Guo JP., Arai T., Miklossy J., McGeer PL. Synapse - Interactions of proteins with an established role in the presynapse. Details of GSK alpha and APP peptides taken from manufacturers' websites mcgeerpl@interchange.ubc.ca Proc. Natl. Acad. Sci. U.S.A. (0027-8424) 2006 IMEx Neurodegeneration - Publications depicting interactions involved in neurodegenerative diseases. Parkinsons - Interactions investigated in the context of Parkinsons disease Apoptosis - Interactions involving proteins with a function related to apoptosis Alzheimers - Interactions investigated in the context of Alzheimers disease Only protein-protein interactions imex curation guo-2006-7 in vitro In vitro comigration in sds comigration in sds page comigration in sds western blot western blot Immuno blot Immuno blot Guo JP., Arai T., Miklossy J., McGeer PL. Synapse - Interactions of proteins with an established role in the presynapse. Details of GSK alpha and APP peptides taken from manufacturers' websites mcgeerpl@interchange.ubc.ca Proc. Natl. Acad. Sci. U.S.A. (0027-8424) 2006 IMEx Neurodegeneration - Publications depicting interactions involved in neurodegenerative diseases. Parkinsons - Interactions investigated in the context of Parkinsons disease Apoptosis - Interactions involving proteins with a function related to apoptosis Alzheimers - Interactions investigated in the context of Alzheimers disease Only protein-protein interactions imex curation guo-2006-5 Abeta and tau form soluble complexes that may promote self aggregation of both into the insoluble forms observed in Alzheimer's disease. human-brain Homo sapiens brain brain Brain [cerebrum] elisa enzyme linked immunosorbent assay ELISA ELISA elisa antibody detection identification by antibody antibody detection Guo JP., Arai T., Miklossy J., McGeer PL. Synapse - Interactions of proteins with an established role in the presynapse. Details of GSK alpha and APP peptides taken from manufacturers' websites mcgeerpl@interchange.ubc.ca Proc. Natl. Acad. Sci. U.S.A. (0027-8424) 2006 IMEx Neurodegeneration - Publications depicting interactions involved in neurodegenerative diseases. Parkinsons - Interactions investigated in the context of Parkinsons disease Apoptosis - Interactions involving proteins with a function related to apoptosis Alzheimers - Interactions investigated in the context of Alzheimers disease Only protein-protein interactions imex curation guo-2006-6 Abeta and tau form soluble complexes that may promote self aggregation of both into the insoluble forms observed in Alzheimer's disease. human-brain-hippocampus Homo sapiens hippocampus brain_hippocampus brain hippocampus confocal microscopy confocal microscopy immunostaining immunostaining Guo JP., Arai T., Miklossy J., McGeer PL. Synapse - Interactions of proteins with an established role in the presynapse. Details of GSK alpha and APP peptides taken from manufacturers' websites mcgeerpl@interchange.ubc.ca Proc. Natl. Acad. Sci. U.S.A. (0027-8424) 2006 IMEx Neurodegeneration - Publications depicting interactions involved in neurodegenerative diseases. Parkinsons - Interactions investigated in the context of Parkinsons disease Apoptosis - Interactions involving proteins with a function related to apoptosis Alzheimers - Interactions investigated in the context of Alzheimers disease Only protein-protein interactions imex curation gsk3a_human Glycogen synthase kinase-3 alpha GSK3A Serine/threonine-protein kinase GSK3A protein protein human Homo sapiens Human MSGGGPSGGGPGGSGRARTSSFAEPGGGGGGGGGGPGGSASGPGGTGGGKASVGAMGGGVGASSSGGGPGGSGGGGSGGPGAGTSFPPPGVKLGRDSGKVTTVVATLGQGPERSQEVAYTDIKVIGNGSFGVVYQARLAETRELVAIKKVLQDKRFKNRELQIMRKLDHCNIVRLRYFFYSSGEKKDELYLNLVLEYVPETVYRVARHFTKAKLTIPILYVKVYMYQLFRSLAYIHSQGVCHRDIKPQNLLVDPDTAVLKLCDFGSAKQLVRGEPNVSYICSRYYRAPELIFGATDYTSSIDVWSAGCVLAELLLGQPIFPGDSGVDQLVEIIKVLGTPTREQIREMNPNYTEFKFPQIKAHPWTKVFKSRTPPEAIALCSSLLEYTPSSRLSPLEACAHSFFDELRCLGTQLPNNRPLPPLFNFSAGELSIQPSLNAILIPPHLRSPAGTTTLTPSSQALTETPTSSDWQSTDATPTLTNSS tau_human Microtubule-associated protein tau MAPT MTBT1 TAU Neurofibrillary tangle protein Paired helical filament-tau MAPTL protein protein human Homo sapiens Human MAEPRQEFEVMEDHAGTYGLGDRKDQGGYTMHQDQEGDTDAGLKESPLQTPTEDGSEEPGSETSDAKSTPTAEDVTAPLVDEGAPGKQAAAQPHTEIPEGTTAEEAGIGDTPSLEDEAAGHVTQEPESGKVVQEGFLREPGPPGLSHQLMSGMPGAPLLPEGPREATRQPSGTGPEDTEGGRHAPELLKHQLLGDLHQEGPPLKGAGGKERPGSKEEVDEDRDVDESSPQDSPPSKASPAQDGRPPQTAAREATSIPGFPAEGAIPLPVDFLSKVSTEIPASEPDGPSVGRAKGQDAPLEFTFHVEITPNVQKEQAHSEEHLGRAAFPGAPGEGPEARGPSLGEDTKEADLPEPSEKQPAAAPRGKPVSRVPQLKARMVSKSKDGTGSDDKKAKTSTRSSAKTLKNRPCLSPKHPTPGSSDPLIQPSSPAVCPEPPSSPKYVSSVTSRTGSSGAKEMKLKGADGKTKIATPRGAAPPGQKGQANATRIPAKTPPAPKTPPSSGEPPKSGDRSGYSSPGSPGTPGSRSRTPSLPTPPTREPKKVAVVRTPPKSPSSAKSRLQTAPVPMPDLKNVKSKIGSTENLKHQPGGGKVQIINKKLDLSNVQSKCGSKDNIKHVPGGGSVQIVYKPVDLSKVTSKCGSLGNIHHKPGGGQVEVKSEKLDFKDRVQSKIGSLDNITHVPGGGNKKIETHKLTFRENAKAKTDHGAEIVYKSPVVSGDTSPRHLSNVSSTGSIDMVDSPQLATLADEVSASLAKQGL a4_human Amyloid-beta precursor protein APP A4 AD1 Alzheimer disease amyloid protein ABPP PreA4 Cerebral vascular amyloid peptide Protease nexin-II APPI Amyloid precursor protein Amyloid-beta A4 protein Alzheimer disease amyloid A4 protein homolog Amyloid-beta (A4) precursor protein protein protein human Homo sapiens Human MLPGLALLLLAAWTARALEVPTDGNAGLLAEPQIAMFCGRLNMHMNVQNGKWDSDPSGTKTCIDTKEGILQYCQEVYPELQITNVVEANQPVTIQNWCKRGRKQCKTHPHFVIPYRCLVGEFVSDALLVPDKCKFLHQERMDVCETHLHWHTVAKETCSEKSTNLHDYGMLLPCGIDKFRGVEFVCCPLAEESDNVDSADAEEDDSDVWWGGADTDYADGSEDKVVEVAEEEEVAEVEEEEADDDEDDEDGDEVEEEAEEPYEEATERTTSIATTTTTTTESVEEVVREVCSEQAETGPCRAMISRWYFDVTEGKCAPFFYGGCGGNRNNFDTEEYCMAVCGSAMSQSLLKTTQEPLARDPVKLPTTAASTPDAVDKYLETPGDENEHAHFQKAKERLEAKHRERMSQVMREWEEAERQAKNLPKADKKAVIQHFQEKVESLEQEAANERQQLVETHMARVEAMLNDRRRLALENYITALQAVPPRPRHVFNMLKKYVRAEQKDRQHTLKHFEHVRMVDPKKAAQIRSQVMTHLRVIYERMNQSLSLLYNVPAVAEEIQDEVDELLQKEQNYSDDVLANMISEPRISYGNDALMPSLTETKTTVELLPVNGEFSLDDLQPWHSFGADSVPANTENEVEPVDARPAADRGLTTRPGSGLTNIKTEEISEVKMDAEFRHDSGYEVHHQKLVFFAEDVGSNKGAIIGLMVGGVVIATVIVITLVMLKKKQYTSIHHGVVEVDAAVTPEERHLSKMQQNGYENPTYKFFEQMQN p05067-pro_0000000092 Amyloid-beta protein 42 Alzheimer disease amyloid protein Cerebral vascular amyloid peptide APP A4 AD1 ABPP PreA4 Protease nexin-II APPI Amyloid precursor protein Amyloid-beta A4 protein Alzheimer disease amyloid A4 protein homolog Amyloid-beta (A4) precursor protein protein protein human Homo sapiens Human DAEFRHDSGYEVHHQKLVFFAEDVGSNKGAIIGLMVGGVVIA 672 713 p05067-pro_0000000093 Amyloid-beta protein 40 APP A4 AD1 ABPP Alzheimer disease amyloid protein Cerebral vascular amyloid peptide PreA4 Protease nexin-II APPI Amyloid precursor protein Amyloid-beta A4 protein Alzheimer disease amyloid A4 protein homolog Amyloid-beta (A4) precursor protein protein protein human Homo sapiens Human DAEFRHDSGYEVHHQKLVFFAEDVGSNKGAIIGLMVGGVV 672 711 p10636-8 Microtubule-associated protein tau Tau-4 MAPT MAPTL MTBT1 TAU Neurofibrillary tangle protein Paired helical filament-tau 2N4R protein protein human Homo sapiens Human MAEPRQEFEVMEDHAGTYGLGDRKDQGGYTMHQDQEGDTDAGLKESPLQTPTEDGSEEPGSETSDAKSTPTAEDVTAPLVDEGAPGKQAAAQPHTEIPEGTTAEEAGIGDTPSLEDEAAGHVTQARMVSKSKDGTGSDDKKAKGADGKTKIATPRGAAPPGQKGQANATRIPAKTPPAPKTPPSSGEPPKSGDRSGYSSPGSPGTPGSRSRTPSLPTPPTREPKKVAVVRTPPKSPSSAKSRLQTAPVPMPDLKNVKSKIGSTENLKHQPGGGKVQIINKKLDLSNVQSKCGSKDNIKHVPGGGSVQIVYKPVDLSKVTSKCGSLGNIHHKPGGGQVEVKSEKLDFKDRVQSKIGSLDNITHVPGGGNKKIETHKLTFRENAKAKTDHGAEIVYKSPVVSGDTSPRHLSNVSSTGSIDMVDSPQLATLADEVSASLAKQGL gska-mapt-1 Phosphorylation of MAPT (Tau) by GSKA 777726 n/a 777733 enzyme enzyme unspecified role unspecified role n-terminal gst tag glutathione s tranferase tag glutathione S-tranferase tag glutathione S-tranferase tag gst tag n-term range n-terminal range n-term range n-term range n-terminal range n-term range false spofr-sf_9 Spodoptera frugiperda insect cells Fall armyworm sf_9 insect cells Derived from pupal ovarian tissue of the fall armyworm Cloned from the parent cell line, IPLB-SF-21-AE (SF-21) derived from immature ovaries of fall armyworm Spodoptera frugiperda pupae cells are susceptible to Baculovirus infection n/a 777734 enzyme target enzyme target substrate substrate unspecified role unspecified role ecoli Escherichia coli (strain K12) phosphorylation phosphorylation reaction phosphorylation false false false Fig. 1C Phosphorylation of MAPT (Tau, P10636) gska-mapt-2 Phosphorylation of MAPT (Tau) by GSKA, stimulation by Beta-amyloid protein 42 777726 n/a 777734 enzyme target enzyme target substrate substrate unspecified role unspecified role ecoli Escherichia coli (strain K12) n/a 777733 enzyme enzyme unspecified role unspecified role n-terminal gst tag glutathione s tranferase tag glutathione S-tranferase tag glutathione S-tranferase tag gst tag n-term range n-terminal range n-term range n-term range n-terminal range n-term range false spofr-sf_9 Spodoptera frugiperda insect cells Fall armyworm sf_9 insect cells Derived from pupal ovarian tissue of the fall armyworm Cloned from the parent cell line, IPLB-SF-21-AE (SF-21) derived from immature ovaries of fall armyworm Spodoptera frugiperda pupae cells are susceptible to Baculovirus infection n/a 777735 stimulator stimulator ancillary ancillary region Beta-amyloid protein 42 sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain false chemical synthesis Chemical synthesis (Chemical synthesis) phosphorylation phosphorylation reaction phosphorylation false false false Fig. 1C Phosphorylation of MAPT (Tau, P10636) Beta-amyloid protein 42 is a more effective stimulator of MAPT phosphorylation by GSKa than Beta-amyloid protein 40 gska-mapt-3 Phosphorylation of MAPT (Tau) by GSKA, stimulation by Beta-amyloid protein 40 777726 n/a 777733 enzyme enzyme unspecified role unspecified role n-terminal gst tag glutathione s tranferase tag glutathione S-tranferase tag glutathione S-tranferase tag gst tag n-term range n-terminal range n-term range n-term range n-terminal range n-term range false spofr-sf_9 Spodoptera frugiperda insect cells Fall armyworm sf_9 insect cells Derived from pupal ovarian tissue of the fall armyworm Cloned from the parent cell line, IPLB-SF-21-AE (SF-21) derived from immature ovaries of fall armyworm Spodoptera frugiperda pupae cells are susceptible to Baculovirus infection n/a 777735 stimulator stimulator ancillary ancillary region Beta-amyloid protein 40 sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain false chemical synthesis Chemical synthesis (Chemical synthesis) n/a 777734 enzyme target enzyme target substrate substrate unspecified role unspecified role ecoli Escherichia coli (strain K12) phosphorylation phosphorylation reaction phosphorylation false false false Fig. 1C Phosphorylation of MAPT (Tau, P10636) Beta-amyloid protein 42 is a more effective stimulator of MAPT phosphorylation by GSKa than Beta-amyloid protein 40 app-mapt-1 Binding of MAPT (Tau) to Beta-amyloid protein 40 777727 n/a 777736 unspecified role unspecified role bait bait chemical synthesis Chemical synthesis (Chemical synthesis) n/a 777734 unspecified role unspecified role prey prey ecoli Escherichia coli (strain K12) direct interaction direct interaction false false false 777727 Supp. Fig. 5 Temp=25C, pH=7.4 KA=2.1E7M-1, KD=4.9E-8M app-mapt-2 Binding of MAPT (Tau) to Beta-amyloid protein 42 777727 n/a 777737 unspecified role unspecified role bait bait chemical synthesis Chemical synthesis (Chemical synthesis) 777727 n/a 777734 unspecified role unspecified role prey prey ecoli Escherichia coli (strain K12) direct interaction direct interaction false false false Supp. Fig. 5 Temp=25C, pH=7.4 KA=1.6E6M-1, KD=6.5E-8M mapt-mapt-1 Homodimerisation of MAPT (Tau) 777727 n/a 777734 unspecified role unspecified role prey prey ecoli Escherichia coli (strain K12) n/a 777734 unspecified role unspecified role bait bait ecoli Escherichia coli (strain K12) direct interaction direct interaction false false false Supp. Fig. 5 Temp=25C, pH=7.4 KA=2.2E4M-1, KD=4.7E-5M a4-mapt-1 Detection of MAPT-APP interaction sites on membrane-bound peptide arrays. 777728 n/a 777734 unspecified role unspecified role prey prey ecoli Escherichia coli (strain K12) n/a 777735 unspecified role unspecified role bait bait region sufficient to bind sufficient binding region sufficient to bind deletion analysis deletion analysis certain certain sequence position certain certain certain sequence position certain false regiion sufficient to bind sufficient binding region sufficient to bind deletion analysis deletion analysis certain certain sequence position certain certain certain sequence position certain false region sufficient to bind sufficient binding region sufficient to bind deletion analysis deletion analysis certain certain sequence position certain certain certain sequence position certain false chemical synthesis Chemical synthesis (Chemical synthesis) direct interaction direct interaction false false false Fig. 2A and Table 1 Pre-phosphorylation of MAPT (Tau) blocked binding to regions 682-687 and 698-703 and inhibited binding to 698-703 a4-mapt-2 Detection of MAPT-APP interaction sites on membrane-bound peptide arrays. 777728 n/a 777738 unspecified role unspecified role prey prey region sufficient to bind sufficient binding region sufficient to bind deletion analysis deletion analysis certain certain sequence position certain certain certain sequence position certain false region sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain false region sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain false region sufficient to bind sufficient binding region sufficient to bind deletion analysis deletion analysis certain certain sequence position certain certain certain sequence position certain false region sufficient to bind sufficient binding region sufficient to bind deletion analysis deletion analysis certain certain sequence position certain certain certain sequence position certain false region sufficient to bind sufficient binding region sufficient to bind deletion analysis deletion analysis certain certain sequence position certain certain certain sequence position certain false region sufficient to bind sufficient binding region sufficient to bind deletion analysis deletion analysis certain certain sequence position certain certain certain sequence position certain false region sufficient to bind sufficient binding region sufficient to bind deletion analysis deletion analysis certain certain sequence position certain certain certain sequence position certain false region sufficient to bind sufficient binding region sufficient to bind deletion analysis deletion analysis certain certain sequence position certain certain certain sequence position certain false region sufficient to bind sufficient binding region sufficient to bind deletion analysis deletion analysis certain certain sequence position certain certain certain sequence position certain false region sufficient to bind sufficient binding region sufficient to bind deletion analysis deletion analysis certain certain sequence position certain certain certain sequence position certain false region sufficient to bind sufficient binding region sufficient to bind deletion analysis deletion analysis certain certain sequence position certain certain certain sequence position certain false region sufficient to bind sufficient binding region sufficient to bind deletion analysis deletion analysis certain certain sequence position certain certain certain sequence position certain false region sufficient to bind sufficient binding region sufficient to bind deletion analysis deletion analysis certain certain sequence position certain certain certain sequence position certain false region sufficient to bind sufficient binding region sufficient to bind deletion analysis deletion analysis certain certain sequence position certain certain certain sequence position certain false region sufficient to bind sufficient binding region sufficient to bind deletion analysis deletion analysis certain certain sequence position certain certain certain sequence position certain false region sufficient to bind sufficient binding region sufficient to bind deletion analysis deletion analysis certain certain sequence position certain certain certain sequence position certain false region sufficient to bind sufficient binding region sufficient to bind deletion analysis deletion analysis certain certain sequence position certain certain certain sequence position certain false region sufficient to bind sufficient binding region sufficient to bind deletion analysis deletion analysis certain certain sequence position certain certain certain sequence position certain false chemical synthesis Chemical synthesis (Chemical synthesis) n/a 777735 unspecified role unspecified role bait bait region sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain false direct interaction direct interaction false false false Fig. 2B and Supp. Table 2 Phosphorylation of Thr-212, Ser-214, Ser-356, and Ser-396 completely blocked APP(AB42) binding. Phosphorylation of Thr-217 and Thr-231 decreased the binding significantly. app-mapt-3 Binding of MAPT (Tau) to Beta-amyloid protein 42 777729 n/a 777736 unspecified role unspecified role bait bait chemical synthesis Chemical synthesis (Chemical synthesis) n/a 777734 unspecified role unspecified role prey prey ecoli Escherichia coli (strain K12) direct interaction direct interaction false false false Supp. Table 4 app-mapt-4 Binding of MAPT (Tau) to Beta-amyloid protein 42 777729 n/a 777734 unspecified role unspecified role bait bait ecoli Escherichia coli (strain K12) n/a 777736 unspecified role unspecified role prey prey chemical synthesis Chemical synthesis (Chemical synthesis) direct interaction direct interaction false false false Supp. Table 4 app-mapt-7 777730 N/A 777736 unspecified role unspecified role neutral component neutral component chemical synthesis Chemical synthesis (Chemical synthesis) N/A 777734 unspecified role unspecified role neutral component neutral component ecoli Escherichia coli (strain K12) direct interaction direct interaction false false false Fig. 1 app-mapt-5 Binding of MAPT (Tau) to APP 777731 n/a 777735 unspecified role unspecified role prey prey n/a 777734 unspecified role unspecified role bait bait ecoli Escherichia coli (strain K12) direct interaction direct interaction false false false Supp. Table 5 app-mapt-6 Colocalisation of MAPT (Tau) with APP 777732 n/a 777735 unspecified role unspecified role neutral component neutral component n/a 777734 unspecified role unspecified role neutral component neutral component ecoli Escherichia coli (strain K12) colocalization colocalization false false false Fig. 4