DOI: 10.1046/j.1471-4159.2001.00102.x. Phosphorylation of thr<sup>668</sup>in the cytoplasmic domain of the Alzheimer's disease amyloid precursor protein by stress‐activated protein kinase 1b (Jun N‐terminal kinase‐3)

Phosphorylation of thr668in the cytoplasmic domain of the Alzheimer's disease amyloid precursor protein by stress‐activated protein kinase 1b (Jun N‐terminal kinase‐3)

10.1046/j.1471-4159.2001.00102.x

Crossref journal-article

Wiley

Journal of Neurochemistry (311)

Abstract

Threonine668(thr668) within the carboxy‐terminus of the Alzheimer's disease amyloid precursor protein (APP) is a knownin vivophosphorylation site. Phosphorylation of APPthr668is believed to regulate APP function and metabolism. Thr668precedes a proline, which suggests that it is targeted for phosphorylation by proline‐directed kinase(s). We have investigated the ability of four major neuronally active proline‐directed kinases, cyclin dependent protein kinase‐5, glycogen synthase kinase‐3β, p42 mitogen‐activated protein kinase and stress‐activated protein kinase‐1b, to phosphorylate APPthr668and report here that SAPK1b induces robust phosphorylation of this site bothin vitroandin vivo. This finding provides a molecular framework to link cellular stresses with APP metabolism in both normal and disease states.

Bibliography

Standen, C. L., Brownlees, J., Grierson, A. J., Kesavapany, S., Lau, K., McLoughlin, D. M., & Miller, C. C. J. (2001). Phosphorylation of thr668in the cytoplasmic domain of the Alzheimerâs disease amyloid precursor protein by stressâactivated protein kinase 1b (Jun Nâterminal kinaseâ3). Journal of Neurochemistry, 76(1), 316â320. Portico.

Authors 7

Claire L. Standen (first)
Janet Brownlees (additional)
Andrew J. Grierson (additional)
Sashi Kesavapany (additional)
Kwok‐Fai Lau (additional)
Declan M. McLoughlin (additional)
Christopher C. J. Miller (additional)

References 23 Referenced 102

10.1523/JNEUROSCI.19-11-04421.1999
10.1046/j.1471-4159.1996.67020699.x
10.1242/jcs.113.3.401
10.1016/s0169-328x(98)00166-1
10.1073/pnas.90.24.12045
10.1016/0169-328x(95)00131-b
10.1046/j.1471-4159.1994.63062324.x
10.1074/jbc.271.48.30404
10.1046/j.1471-4159.1998.70010335.x / J. Neurochem. / Cyclin D2 interacts with cdk‐5 and modulates cellular cdk‐5/p35 activity by Guidato S. (1998)
10.1046/j.1471-4159.1996.66041698.x
10.1046/j.1471-4159.2000.0751085.x
10.1042/bj3300029
10.1016/S0021-9258(18)34041-9 / J. Biol. Chem. / Multiple phosphorylation sites in mammalian neurofilament polypeptides by Julien J.‐P. (1982)
10.1016/S0960-9822(00)00246-3
10.1016/0169-328x(95)00181-q
10.1016/s0014-5793(96)01128-3
10.1007/BF03401803
10.1016/s0962-8924(98)01363-4
10.1074/jbc.271.24.14245
10.1002/j.1460-2075.1994.tb06360.x
10.1242/dev.119.4.1029
10.1523/JNEUROSCI.18-11-04008.1998 / J. Neurosci. / Mitogen‐activated protein kinases (Erk1,2) phosphorylate Lys‐Ser‐Pro (KSP) repeats in neurofilament proteins NF‐H and NF‐M by Veeranna Amin N. D. (1998)
10.1038/nm0795-693

Dates

Type	When
Created	22 years, 5 months ago (March 12, 2003, 1:49 a.m.)
Deposited	1 year, 7 months ago (Jan. 3, 2024, 12:59 p.m.)
Indexed	1 month, 3 weeks ago (July 7, 2025, 1:25 a.m.)
Issued	24 years, 7 months ago (Jan. 1, 2001)
Published	24 years, 7 months ago (Jan. 1, 2001)
Published Online	16 years, 4 months ago (April 22, 2009)
Published Print	24 years, 7 months ago (Jan. 1, 2001)

Funders 0

None

BibTeX

@article{Standen_2001, title={Phosphorylation of thr668in the cytoplasmic domain of the Alzheimer’s disease amyloid precursor protein by stress‐activated protein kinase 1b (Jun N‐terminal kinase‐3)}, volume={76}, ISSN={1471-4159}, url={http://dx.doi.org/10.1046/j.1471-4159.2001.00102.x}, DOI={10.1046/j.1471-4159.2001.00102.x}, number={1}, journal={Journal of Neurochemistry}, publisher={Wiley}, author={Standen, Claire L. and Brownlees, Janet and Grierson, Andrew J. and Kesavapany, Sashi and Lau, Kwok‐Fai and McLoughlin, Declan M. and Miller, Christopher C. J.}, year={2001}, month=jan, pages={316–320} }

JSON

{
  "indexed": {
    "date-parts": [
      [
        2025,
        7,
        7
      ]
    ],
    "date-time": "2025-07-07T05:25:05Z",
    "timestamp": 1751865905615
  },
  "reference-count": 23,
  "publisher": "Wiley",
  "issue": "1",
  "license": [
    {
      "start": {
        "date-parts": [
          [
            2009,
            4,
            22
          ]
        ],
        "date-time": "2009-04-22T00:00:00Z",
        "timestamp": 1240358400000
      },
      "content-version": "vor",
      "delay-in-days": 3033,
      "URL": "http://onlinelibrary.wiley.com/termsAndConditions#vor"
    }
  ],
  "content-domain": {
    "domain": [],
    "crossmark-restriction": false
  },
  "published-print": {
    "date-parts": [
      [
        2001,
        1
      ]
    ]
  },
  "abstract": "<jats:p>Threonine<jats:sup>668</jats:sup>(thr<jats:sup>668</jats:sup>) within the carboxy\u2010terminus of the Alzheimer's disease amyloid precursor protein (APP) is a known<jats:italic>in vivo</jats:italic>phosphorylation site. Phosphorylation of APPthr<jats:sup>668</jats:sup>is believed to regulate APP function and metabolism. Thr<jats:sup>668</jats:sup>precedes a proline, which suggests that it is targeted for phosphorylation by proline\u2010directed kinase(s). We have investigated the ability of four major neuronally active proline\u2010directed kinases, cyclin dependent protein kinase\u20105, glycogen synthase kinase\u20103\u03b2, p42 mitogen\u2010activated protein kinase and stress\u2010activated protein kinase\u20101b, to phosphorylate APPthr<jats:sup>668</jats:sup>and report here that SAPK1b induces robust phosphorylation of this site both<jats:italic>in vitro</jats:italic>and<jats:italic>in vivo</jats:italic>. This finding provides a molecular framework to link cellular stresses with APP metabolism in both normal and disease states.</jats:p>",
  "DOI": "10.1046/j.1471-4159.2001.00102.x",
  "type": "journal-article",
  "created": {
    "date-parts": [
      [
        2003,
        3,
        12
      ]
    ],
    "date-time": "2003-03-12T06:49:57Z",
    "timestamp": 1047451797000
  },
  "page": "316-320",
  "source": "Crossref",
  "is-referenced-by-count": 102,
  "title": "Phosphorylation of thr<sup>668</sup>in the cytoplasmic domain of the Alzheimer's disease amyloid precursor protein by stress\u2010activated protein kinase 1b (Jun N\u2010terminal kinase\u20103)",
  "prefix": "10.1111",
  "volume": "76",
  "author": [
    {
      "given": "Claire L.",
      "family": "Standen",
      "sequence": "first",
      "affiliation": []
    },
    {
      "given": "Janet",
      "family": "Brownlees",
      "sequence": "additional",
      "affiliation": []
    },
    {
      "given": "Andrew J.",
      "family": "Grierson",
      "sequence": "additional",
      "affiliation": []
    },
    {
      "given": "Sashi",
      "family": "Kesavapany",
      "sequence": "additional",
      "affiliation": []
    },
    {
      "given": "Kwok\u2010Fai",
      "family": "Lau",
      "sequence": "additional",
      "affiliation": []
    },
    {
      "given": "Declan M.",
      "family": "McLoughlin",
      "sequence": "additional",
      "affiliation": []
    },
    {
      "given": "Christopher C. J.",
      "family": "Miller",
      "sequence": "additional",
      "affiliation": []
    }
  ],
  "member": "311",
  "published-online": {
    "date-parts": [
      [
        2009,
        4,
        22
      ]
    ]
  },
  "reference": [
    {
      "key": "e_1_2_6_2_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1523/JNEUROSCI.19-11-04421.1999"
    },
    {
      "key": "e_1_2_6_3_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1046/j.1471-4159.1996.67020699.x"
    },
    {
      "key": "e_1_2_6_4_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1242/jcs.113.3.401"
    },
    {
      "key": "e_1_2_6_5_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/s0169-328x(98)00166-1"
    },
    {
      "key": "e_1_2_6_6_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.90.24.12045"
    },
    {
      "key": "e_1_2_6_7_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0169-328x(95)00131-b"
    },
    {
      "key": "e_1_2_6_8_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1046/j.1471-4159.1994.63062324.x"
    },
    {
      "key": "e_1_2_6_9_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.271.48.30404"
    },
    {
      "key": "e_1_2_6_10_1",
      "doi-asserted-by": "crossref",
      "first-page": "492",
      "DOI": "10.1046/j.1471-4159.1998.70010335.x",
      "article-title": "Cyclin D2 interacts with cdk\u20105 and modulates cellular cdk\u20105/p35 activity",
      "volume": "70",
      "author": "Guidato S.",
      "year": "1998",
      "journal-title": "J. Neurochem."
    },
    {
      "key": "e_1_2_6_11_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1046/j.1471-4159.1996.66041698.x"
    },
    {
      "key": "e_1_2_6_12_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1046/j.1471-4159.2000.0751085.x"
    },
    {
      "key": "e_1_2_6_13_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1042/bj3300029"
    },
    {
      "key": "e_1_2_6_14_1",
      "doi-asserted-by": "crossref",
      "first-page": "10467",
      "DOI": "10.1016/S0021-9258(18)34041-9",
      "article-title": "Multiple phosphorylation sites in mammalian neurofilament polypeptides",
      "volume": "257",
      "author": "Julien J.\u2010P.",
      "year": "1982",
      "journal-title": "J. Biol. Chem."
    },
    {
      "key": "e_1_2_6_15_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0960-9822(00)00246-3"
    },
    {
      "key": "e_1_2_6_16_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0169-328x(95)00181-q"
    },
    {
      "key": "e_1_2_6_17_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/s0014-5793(96)01128-3"
    },
    {
      "key": "e_1_2_6_18_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1007/BF03401803"
    },
    {
      "key": "e_1_2_6_19_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/s0962-8924(98)01363-4"
    },
    {
      "key": "e_1_2_6_20_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.271.24.14245"
    },
    {
      "key": "e_1_2_6_21_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/j.1460-2075.1994.tb06360.x"
    },
    {
      "key": "e_1_2_6_22_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1242/dev.119.4.1029"
    },
    {
      "key": "e_1_2_6_23_1",
      "doi-asserted-by": "crossref",
      "first-page": "4008",
      "DOI": "10.1523/JNEUROSCI.18-11-04008.1998",
      "article-title": "Mitogen\u2010activated protein kinases (Erk1,2) phosphorylate Lys\u2010Ser\u2010Pro (KSP) repeats in neurofilament proteins NF\u2010H and NF\u2010M",
      "volume": "18",
      "author": "Veeranna Amin N. D.",
      "year": "1998",
      "journal-title": "J. Neurosci."
    },
    {
      "key": "e_1_2_6_24_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/nm0795-693"
    }
  ],
  "container-title": "Journal of Neurochemistry",
  "original-title": [],
  "language": "en",
  "link": [
    {
      "URL": "https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1046%2Fj.1471-4159.2001.00102.x",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "text-mining"
    },
    {
      "URL": "https://onlinelibrary.wiley.com/doi/pdf/10.1046/j.1471-4159.2001.00102.x",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "similarity-checking"
    }
  ],
  "deposited": {
    "date-parts": [
      [
        2024,
        1,
        3
      ]
    ],
    "date-time": "2024-01-03T17:59:33Z",
    "timestamp": 1704304773000
  },
  "score": 1,
  "resource": {
    "primary": {
      "URL": "https://onlinelibrary.wiley.com/doi/10.1046/j.1471-4159.2001.00102.x"
    }
  },
  "subtitle": [],
  "short-title": [],
  "issued": {
    "date-parts": [
      [
        2001,
        1
      ]
    ]
  },
  "references-count": 23,
  "journal-issue": {
    "issue": "1",
    "published-print": {
      "date-parts": [
        [
          2001,
          1
        ]
      ]
    }
  },
  "alternative-id": [
    "10.1046/j.1471-4159.2001.00102.x"
  ],
  "URL": "http://dx.doi.org/10.1046/j.1471-4159.2001.00102.x",
  "relation": {},
  "ISSN": [
    "0022-3042",
    "1471-4159"
  ],
  "subject": [],
  "container-title-short": "Journal of Neurochemistry",
  "published": {
    "date-parts": [
      [
        2001,
        1
      ]
    ]
  }
}