DOI: 10.4049/jimmunol.177.3.1772. A Protein Associated with Toll-Like Receptor 4 (PRAT4A) Regulates Cell Surface Expression of TLR4

A Protein Associated with Toll-Like Receptor 4 (PRAT4A) Regulates Cell Surface Expression of TLR4

10.4049/jimmunol.177.3.1772

Crossref journal-article

Oxford University Press (OUP)

The Journal of Immunology (286)

Abstract

Abstract TLRs recognize microbial products. Their subcellular distribution is optimized for microbial recognition. Little is known, however, about mechanisms regulating the subcellular distribution of TLRs. LPS is recognized by the receptor complex consisting of TLR4 and MD-2. Although MD-2, a coreceptor for TLR4, enhances cell surface expression of TLR4, an additional mechanism regulating TLR4 distribution has been suggested. We show here that PRAT4A, a novel protein associated with TLR4, regulates cell surface expression of TLR4. PRAT4A is associated with the immature form of TLR4 but not with MD-2 or TLR2. PRAT4A knockdown abolished LPS responsiveness in a cell line expressing TLR4/MD-2, probably due to the lack of cell surface TLR4. PRAT4A knockdown down-regulated cell surface TLR4/MD-2 on dendritic cells. These results demonstrate a novel mechanism regulating TLR4/MD-2 expression on the cell surface.

Bibliography

Wakabayashi, Y., Kobayashi, M., Akashi-Takamura, S., Tanimura, N., Konno, K., Takahashi, K., Ishii, T., Mizutani, T., Iba, H., Kouro, T., Takaki, S., Takatsu, K., Oda, Y., Ishihama, Y., Saitoh, S., & Miyake, K. (2006). A Protein Associated with Toll-Like Receptor 4 (PRAT4A) Regulates Cell Surface Expression of TLR4. The Journal of Immunology, 177(3), 1772â1779.

Authors 16

Yasutaka Wakabayashi (first)
Makiko Kobayashi (additional)
Sachiko Akashi-Takamura (additional)
Natsuko Tanimura (additional)
Kazunori Konno (additional)
Koichiro Takahashi (additional)
Takashi Ishii (additional)
Taketoshi Mizutani (additional)
Hideo Iba (additional)
Taku Kouro (additional)
Satoshi Takaki (additional)
Kiyoshi Takatsu (additional)
Yoshiya Oda (additional)
Yasushi Ishihama (additional)
Shin-ichiroh Saitoh (additional)
Kensuke Miyake (additional)

References 30 Referenced 93

{'first-page': '197', 'volume-title': 'Annu. Rev. Immunol.', 'year': '2002', 'key': '2025032807155272500_R1'} / Annu. Rev. Immunol. (2002)
{'first-page': '335', 'volume-title': 'Annu. Rev. Immunol.', 'year': '2003', 'key': '2025032807155272500_R2'} / Annu. Rev. Immunol. (2003)
{'first-page': '394', 'volume-title': 'Nature', 'year': '1997', 'key': '2025032807155272500_R3'} / Nature (1997)
{'first-page': '1882', 'volume-title': 'J. Immunol.', 'year': '2001', 'key': '2025032807155272500_R4'} / J. Immunol. (2001)
{'first-page': '49', 'volume-title': 'Nat. Immunol.', 'year': '2006', 'key': '2025032807155272500_R5'} / Nat. Immunol. (2006)
{'first-page': '2154', 'volume-title': 'Eur. J. Immunol.', 'year': '2001', 'key': '2025032807155272500_R6'} / Eur. J. Immunol. (2001)
{'first-page': '2372', 'volume-title': 'J. Immunol.', 'year': '2001', 'key': '2025032807155272500_R7'} / J. Immunol. (2001)
{'first-page': '1035', 'volume-title': 'Nature', 'year': '2005', 'key': '2025032807155272500_R8'} / Nature (2005)
{'first-page': '190', 'volume-title': 'Nat. Immunol.', 'year': '2004', 'key': '2025032807155272500_R9'} / Nat. Immunol. (2004)
{'first-page': '34698', 'volume-title': 'J. Biol. Chem.', 'year': '2004', 'key': '2025032807155272500_R10'} / J. Biol. Chem. (2004)
{'first-page': '2085', 'volume-title': 'Science', 'year': '1998', 'key': '2025032807155272500_R11'} / Science (1998)
{'first-page': '615', 'volume-title': 'J. Exp. Med.', 'year': '1999', 'key': '2025032807155272500_R12'} / J. Exp. Med. (1999)
{'first-page': '3749', 'volume-title': 'J. Immunol.', 'year': '1999', 'key': '2025032807155272500_R13'} / J. Immunol. (1999)
{'first-page': '10689', 'volume-title': 'J. Biol. Chem.', 'year': '1999', 'key': '2025032807155272500_R14'} / J. Biol. Chem. (1999)
{'first-page': '1777', 'volume-title': 'J. Exp. Med.', 'year': '1999', 'key': '2025032807155272500_R15'} / J. Exp. Med. (1999)
{'first-page': '1699', 'volume-title': 'Blood', 'year': '2002', 'key': '2025032807155272500_R16'} / Blood (2002)
{'first-page': '79', 'volume-title': 'J. Exp. Med.', 'year': '2001', 'key': '2025032807155272500_R17'} / J. Exp. Med. (2001)
{'first-page': '389', 'volume-title': 'J. Endotoxin Res.', 'year': '2000', 'key': '2025032807155272500_R18'} / J. Endotoxin Res. (2000)
{'first-page': '1035', 'volume-title': 'J. Exp. Med.', 'year': '2003', 'key': '2025032807155272500_R19'} / J. Exp. Med. (2003)
{'first-page': '1225', 'volume-title': 'J. Exp. Med.', 'year': '2003', 'key': '2025032807155272500_R20'} / J. Exp. Med. (2003)
{'first-page': '47834', 'volume-title': 'J. Biol. Chem.', 'year': '2002', 'key': '2025032807155272500_R21'} / J. Biol. Chem. (2002)
{'first-page': '891', 'volume-title': 'Nat. Cell Biol.', 'year': '2001', 'key': '2025032807155272500_R22'} / Nat. Cell Biol. (2001)
{'first-page': '405', 'volume-title': 'Clin. Diagn. Lab. Immunol.', 'year': '2003', 'key': '2025032807155272500_R23'} / Clin. Diagn. Lab. Immunol. (2003)
{'first-page': 'L428', 'volume-title': 'Am. J. Physiol.', 'year': '2004', 'key': '2025032807155272500_R24'} / Am. J. Physiol. (2004)
{'first-page': '4186', 'volume-title': 'Proc. Natl. Acad. Sci. USA', 'year': '2004', 'key': '2025032807155272500_R25'} / Proc. Natl. Acad. Sci. USA (2004)
{'first-page': '5471', 'volume-title': 'Oncogene', 'year': '2005', 'key': '2025032807155272500_R26'} / Oncogene (2005)
{'first-page': '3471', 'volume-title': 'J. Immunol.', 'year': '2000', 'key': '2025032807155272500_R27'} / J. Immunol. (2000)
{'first-page': '114', 'volume-title': 'Hum. Genet.', 'year': '1997', 'key': '2025032807155272500_R28'} / Hum. Genet. (1997)
{'first-page': '27', 'volume-title': 'Mol. Endocrinol.', 'year': '2003', 'key': '2025032807155272500_R29'} / Mol. Endocrinol. (2003)
{'first-page': '1076', 'volume-title': 'Biochem. Biophys. Res. Commun.', 'year': '2006', 'key': '2025032807155272500_R30'} / Biochem. Biophys. Res. Commun. (2006)

Dates

Type	When
Created	11 years, 4 months ago (April 24, 2014, 12:59 p.m.)
Deposited	5 months ago (March 30, 2025, 6:56 p.m.)
Indexed	2 weeks, 2 days ago (Aug. 20, 2025, 8:58 a.m.)
Issued	19 years, 1 month ago (Aug. 1, 2006)
Published	19 years, 1 month ago (Aug. 1, 2006)
Published Online	19 years, 1 month ago (Aug. 1, 2006)
Published Print	19 years, 1 month ago (Aug. 1, 2006)

Funders 0

None

BibTeX

@article{Wakabayashi_2006, title={A Protein Associated with Toll-Like Receptor 4 (PRAT4A) Regulates Cell Surface Expression of TLR4}, volume={177}, ISSN={1550-6606}, url={http://dx.doi.org/10.4049/jimmunol.177.3.1772}, DOI={10.4049/jimmunol.177.3.1772}, number={3}, journal={The Journal of Immunology}, publisher={Oxford University Press (OUP)}, author={Wakabayashi, Yasutaka and Kobayashi, Makiko and Akashi-Takamura, Sachiko and Tanimura, Natsuko and Konno, Kazunori and Takahashi, Koichiro and Ishii, Takashi and Mizutani, Taketoshi and Iba, Hideo and Kouro, Taku and Takaki, Satoshi and Takatsu, Kiyoshi and Oda, Yoshiya and Ishihama, Yasushi and Saitoh, Shin-ichiroh and Miyake, Kensuke}, year={2006}, month=aug, pages={1772–1779} }

JSON

{
  "indexed": {
    "date-parts": [
      [
        2025,
        8,
        20
      ]
    ],
    "date-time": "2025-08-20T12:58:57Z",
    "timestamp": 1755694737392,
    "version": "3.40.3"
  },
  "reference-count": 30,
  "publisher": "Oxford University Press (OUP)",
  "issue": "3",
  "license": [
    {
      "start": {
        "date-parts": [
          [
            2006,
            8,
            1
          ]
        ],
        "date-time": "2006-08-01T00:00:00Z",
        "timestamp": 1154390400000
      },
      "content-version": "vor",
      "delay-in-days": 0,
      "URL": "https://academic.oup.com/pages/standard-publication-reuse-rights"
    }
  ],
  "content-domain": {
    "domain": [],
    "crossmark-restriction": false
  },
  "published-print": {
    "date-parts": [
      [
        2006,
        8,
        1
      ]
    ]
  },
  "abstract": "<jats:title>Abstract</jats:title>\n               <jats:p>TLRs recognize microbial products. Their subcellular distribution is optimized for microbial recognition. Little is known, however, about mechanisms regulating the subcellular distribution of TLRs. LPS is recognized by the receptor complex consisting of TLR4 and MD-2. Although MD-2, a coreceptor for TLR4, enhances cell surface expression of TLR4, an additional mechanism regulating TLR4 distribution has been suggested. We show here that PRAT4A, a novel protein associated with TLR4, regulates cell surface expression of TLR4. PRAT4A is associated with the immature form of TLR4 but not with MD-2 or TLR2. PRAT4A knockdown abolished LPS responsiveness in a cell line expressing TLR4/MD-2, probably due to the lack of cell surface TLR4. PRAT4A knockdown down-regulated cell surface TLR4/MD-2 on dendritic cells. These results demonstrate a novel mechanism regulating TLR4/MD-2 expression on the cell surface.</jats:p>",
  "DOI": "10.4049/jimmunol.177.3.1772",
  "type": "journal-article",
  "created": {
    "date-parts": [
      [
        2014,
        4,
        24
      ]
    ],
    "date-time": "2014-04-24T16:59:02Z",
    "timestamp": 1398358742000
  },
  "page": "1772-1779",
  "source": "Crossref",
  "is-referenced-by-count": 93,
  "title": "A Protein Associated with Toll-Like Receptor 4 (PRAT4A) Regulates Cell Surface Expression of TLR4",
  "prefix": "10.1093",
  "volume": "177",
  "author": [
    {
      "given": "Yasutaka",
      "family": "Wakabayashi",
      "sequence": "first",
      "affiliation": [
        {
          "name": "Division of Infectious Genetics, University of Tokyo , Tokyo ,",
          "place": [
            "Japan"
          ]
        }
      ]
    },
    {
      "given": "Makiko",
      "family": "Kobayashi",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Division of Infectious Genetics, University of Tokyo , Tokyo ,",
          "place": [
            "Japan"
          ]
        }
      ]
    },
    {
      "given": "Sachiko",
      "family": "Akashi-Takamura",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Division of Infectious Genetics, University of Tokyo , Tokyo ,",
          "place": [
            "Japan"
          ]
        }
      ]
    },
    {
      "given": "Natsuko",
      "family": "Tanimura",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Division of Infectious Genetics, University of Tokyo , Tokyo ,",
          "place": [
            "Japan"
          ]
        }
      ]
    },
    {
      "given": "Kazunori",
      "family": "Konno",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Division of Infectious Genetics, University of Tokyo , Tokyo ,",
          "place": [
            "Japan"
          ]
        }
      ]
    },
    {
      "given": "Koichiro",
      "family": "Takahashi",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Division of Infectious Genetics, University of Tokyo , Tokyo ,",
          "place": [
            "Japan"
          ]
        }
      ]
    },
    {
      "given": "Takashi",
      "family": "Ishii",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Division of Infectious Genetics, University of Tokyo , Tokyo ,",
          "place": [
            "Japan"
          ]
        }
      ]
    },
    {
      "given": "Taketoshi",
      "family": "Mizutani",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Division of Host-Parasite Interaction, University of Tokyo , Tokyo ,",
          "place": [
            "Japan"
          ]
        }
      ]
    },
    {
      "given": "Hideo",
      "family": "Iba",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Division of Host-Parasite Interaction, University of Tokyo , Tokyo ,",
          "place": [
            "Japan"
          ]
        }
      ]
    },
    {
      "given": "Taku",
      "family": "Kouro",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Division of Immunology, Institute of Medical Science, University of Tokyo , Tokyo ,",
          "place": [
            "Japan"
          ]
        }
      ]
    },
    {
      "given": "Satoshi",
      "family": "Takaki",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Division of Immunology, Institute of Medical Science, University of Tokyo , Tokyo ,",
          "place": [
            "Japan"
          ]
        }
      ]
    },
    {
      "given": "Kiyoshi",
      "family": "Takatsu",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Division of Immunology, Institute of Medical Science, University of Tokyo , Tokyo ,",
          "place": [
            "Japan"
          ]
        }
      ]
    },
    {
      "given": "Yoshiya",
      "family": "Oda",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Laboratory of Seeds Finding Technology, Eisai Co. Ltd. , Tsukuba ,",
          "place": [
            "Japan"
          ]
        }
      ]
    },
    {
      "given": "Yasushi",
      "family": "Ishihama",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Laboratory of Seeds Finding Technology, Eisai Co. Ltd. , Tsukuba ,",
          "place": [
            "Japan"
          ]
        }
      ]
    },
    {
      "given": "Shin-ichiroh",
      "family": "Saitoh",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Division of Infectious Genetics, University of Tokyo , Tokyo ,",
          "place": [
            "Japan"
          ]
        }
      ]
    },
    {
      "given": "Kensuke",
      "family": "Miyake",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Division of Infectious Genetics, University of Tokyo , Tokyo ,",
          "place": [
            "Japan"
          ]
        },
        {
          "name": "Core Research for Engineering, Science, and Technology, Japan Science and Technology Corporation , Tokyo ,",
          "place": [
            "Japan"
          ]
        }
      ]
    }
  ],
  "member": "286",
  "published-online": {
    "date-parts": [
      [
        2006,
        8,
        1
      ]
    ]
  },
  "reference": [
    {
      "first-page": "197",
      "volume-title": "Annu. Rev. Immunol.",
      "year": "2002",
      "key": "2025032807155272500_R1"
    },
    {
      "first-page": "335",
      "volume-title": "Annu. Rev. Immunol.",
      "year": "2003",
      "key": "2025032807155272500_R2"
    },
    {
      "first-page": "394",
      "volume-title": "Nature",
      "year": "1997",
      "key": "2025032807155272500_R3"
    },
    {
      "first-page": "1882",
      "volume-title": "J. Immunol.",
      "year": "2001",
      "key": "2025032807155272500_R4"
    },
    {
      "first-page": "49",
      "volume-title": "Nat. Immunol.",
      "year": "2006",
      "key": "2025032807155272500_R5"
    },
    {
      "first-page": "2154",
      "volume-title": "Eur. J. Immunol.",
      "year": "2001",
      "key": "2025032807155272500_R6"
    },
    {
      "first-page": "2372",
      "volume-title": "J. Immunol.",
      "year": "2001",
      "key": "2025032807155272500_R7"
    },
    {
      "first-page": "1035",
      "volume-title": "Nature",
      "year": "2005",
      "key": "2025032807155272500_R8"
    },
    {
      "first-page": "190",
      "volume-title": "Nat. Immunol.",
      "year": "2004",
      "key": "2025032807155272500_R9"
    },
    {
      "first-page": "34698",
      "volume-title": "J. Biol. Chem.",
      "year": "2004",
      "key": "2025032807155272500_R10"
    },
    {
      "first-page": "2085",
      "volume-title": "Science",
      "year": "1998",
      "key": "2025032807155272500_R11"
    },
    {
      "first-page": "615",
      "volume-title": "J. Exp. Med.",
      "year": "1999",
      "key": "2025032807155272500_R12"
    },
    {
      "first-page": "3749",
      "volume-title": "J. Immunol.",
      "year": "1999",
      "key": "2025032807155272500_R13"
    },
    {
      "first-page": "10689",
      "volume-title": "J. Biol. Chem.",
      "year": "1999",
      "key": "2025032807155272500_R14"
    },
    {
      "first-page": "1777",
      "volume-title": "J. Exp. Med.",
      "year": "1999",
      "key": "2025032807155272500_R15"
    },
    {
      "first-page": "1699",
      "volume-title": "Blood",
      "year": "2002",
      "key": "2025032807155272500_R16"
    },
    {
      "first-page": "79",
      "volume-title": "J. Exp. Med.",
      "year": "2001",
      "key": "2025032807155272500_R17"
    },
    {
      "first-page": "389",
      "volume-title": "J. Endotoxin Res.",
      "year": "2000",
      "key": "2025032807155272500_R18"
    },
    {
      "first-page": "1035",
      "volume-title": "J. Exp. Med.",
      "year": "2003",
      "key": "2025032807155272500_R19"
    },
    {
      "first-page": "1225",
      "volume-title": "J. Exp. Med.",
      "year": "2003",
      "key": "2025032807155272500_R20"
    },
    {
      "first-page": "47834",
      "volume-title": "J. Biol. Chem.",
      "year": "2002",
      "key": "2025032807155272500_R21"
    },
    {
      "first-page": "891",
      "volume-title": "Nat. Cell Biol.",
      "year": "2001",
      "key": "2025032807155272500_R22"
    },
    {
      "first-page": "405",
      "volume-title": "Clin. Diagn. Lab. Immunol.",
      "year": "2003",
      "key": "2025032807155272500_R23"
    },
    {
      "first-page": "L428",
      "volume-title": "Am. J. Physiol.",
      "year": "2004",
      "key": "2025032807155272500_R24"
    },
    {
      "first-page": "4186",
      "volume-title": "Proc. Natl. Acad. Sci. USA",
      "year": "2004",
      "key": "2025032807155272500_R25"
    },
    {
      "first-page": "5471",
      "volume-title": "Oncogene",
      "year": "2005",
      "key": "2025032807155272500_R26"
    },
    {
      "first-page": "3471",
      "volume-title": "J. Immunol.",
      "year": "2000",
      "key": "2025032807155272500_R27"
    },
    {
      "first-page": "114",
      "volume-title": "Hum. Genet.",
      "year": "1997",
      "key": "2025032807155272500_R28"
    },
    {
      "first-page": "27",
      "volume-title": "Mol. Endocrinol.",
      "year": "2003",
      "key": "2025032807155272500_R29"
    },
    {
      "first-page": "1076",
      "volume-title": "Biochem. Biophys. Res. Commun.",
      "year": "2006",
      "key": "2025032807155272500_R30"
    }
  ],
  "container-title": "The Journal of Immunology",
  "original-title": [],
  "language": "en",
  "link": [
    {
      "URL": "https://academic.oup.com/jimmunol/article-pdf/177/3/1772/62645234/zim01506001772.pdf",
      "content-type": "application/pdf",
      "content-version": "vor",
      "intended-application": "syndication"
    },
    {
      "URL": "https://academic.oup.com/jimmunol/article-pdf/177/3/1772/62645234/zim01506001772.pdf",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "similarity-checking"
    }
  ],
  "deposited": {
    "date-parts": [
      [
        2025,
        3,
        30
      ]
    ],
    "date-time": "2025-03-30T22:56:48Z",
    "timestamp": 1743375408000
  },
  "score": 1,
  "resource": {
    "primary": {
      "URL": "https://academic.oup.com/jimmunol/article/177/3/1772/8059488"
    }
  },
  "subtitle": [],
  "short-title": [],
  "issued": {
    "date-parts": [
      [
        2006,
        8,
        1
      ]
    ]
  },
  "references-count": 30,
  "journal-issue": {
    "issue": "3",
    "published-print": {
      "date-parts": [
        [
          2006,
          8,
          1
        ]
      ]
    }
  },
  "URL": "http://dx.doi.org/10.4049/jimmunol.177.3.1772",
  "relation": {},
  "ISSN": [
    "0022-1767",
    "1550-6606"
  ],
  "subject": [],
  "published-other": {
    "date-parts": [
      [
        2006,
        8
      ]
    ]
  },
  "published": {
    "date-parts": [
      [
        2006,
        8,
        1
      ]
    ]
  }
}