DOI: 10.1126/science.2237442. A Cytoplasmic Protein Inhibits the GTPase Activity of H-Ras in a Phospholipid-Dependent Manner

A Cytoplasmic Protein Inhibits the GTPase Activity of H-Ras in a Phospholipid-Dependent Manner

10.1126/science.2237442

Crossref journal-article

American Association for the Advancement of Science (AAAS)

Science (221)

Abstract

A cytoplasmic protein has been identified that inhibits the guanosine triphosphatase (GTPase) activity of bacterially synthesized, cellular H-Ras protein. This GTPase inhibiting protein is able to counteract the activity of GTPase activating protein (GAP), which has been postulated to function as a negative regulator of Ras activity. The potential biological importance of the GTPase inhibiting protein is further supported by its interaction with lipids. Phospholipids produced in cells as a consequence of mitogenic stimulation increase the activity of the GTPase inhibiting protein, as well as inhibit the activity of GAP. The interaction of such lipids with each of these two regulatory proteins would, therefore, tend to increase the biological activity of Ras and stimulate cell proliferation.

Bibliography

Tsai, M.-H., Yu, C.-L., & Stacey, D. W. (1990). A Cytoplasmic Protein Inhibits the GTPase Activity of H-Ras in a Phospholipid-Dependent Manner. Science, 250(4983), 982â985.

Authors 3

Men-Hwei Tsai (first)
Chun-Li Yu (additional)
Dennis W. Stacey (additional)

References 22 Referenced 119

Dates

Type	When
Created	18 years, 10 months ago (Oct. 5, 2006, 6:10 p.m.)
Deposited	1 year, 7 months ago (Jan. 12, 2024, 4:51 a.m.)
Indexed	1 month, 4 weeks ago (July 2, 2025, 2:46 p.m.)
Issued	34 years, 9 months ago (Nov. 16, 1990)
Published	34 years, 9 months ago (Nov. 16, 1990)
Published Print	34 years, 9 months ago (Nov. 16, 1990)

Funders 0

None

BibTeX

@article{Tsai_1990, title={A Cytoplasmic Protein Inhibits the GTPase Activity of H-Ras in a Phospholipid-Dependent Manner}, volume={250}, ISSN={1095-9203}, url={http://dx.doi.org/10.1126/science.2237442}, DOI={10.1126/science.2237442}, number={4983}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Tsai, Men-Hwei and Yu, Chun-Li and Stacey, Dennis W.}, year={1990}, month=nov, pages={982–985} }

JSON

{
  "indexed": {
    "date-parts": [
      [
        2025,
        7,
        2
      ]
    ],
    "date-time": "2025-07-02T18:46:32Z",
    "timestamp": 1751481992958
  },
  "reference-count": 22,
  "publisher": "American Association for the Advancement of Science (AAAS)",
  "issue": "4983",
  "content-domain": {
    "domain": [],
    "crossmark-restriction": false
  },
  "published-print": {
    "date-parts": [
      [
        1990,
        11,
        16
      ]
    ]
  },
  "abstract": "<jats:p>A cytoplasmic protein has been identified that inhibits the guanosine triphosphatase (GTPase) activity of bacterially synthesized, cellular H-Ras protein. This GTPase inhibiting protein is able to counteract the activity of GTPase activating protein (GAP), which has been postulated to function as a negative regulator of Ras activity. The potential biological importance of the GTPase inhibiting protein is further supported by its interaction with lipids. Phospholipids produced in cells as a consequence of mitogenic stimulation increase the activity of the GTPase inhibiting protein, as well as inhibit the activity of GAP. The interaction of such lipids with each of these two regulatory proteins would, therefore, tend to increase the biological activity of Ras and stimulate cell proliferation.</jats:p>",
  "DOI": "10.1126/science.2237442",
  "type": "journal-article",
  "created": {
    "date-parts": [
      [
        2006,
        10,
        5
      ]
    ],
    "date-time": "2006-10-05T22:10:14Z",
    "timestamp": 1160086214000
  },
  "page": "982-985",
  "source": "Crossref",
  "is-referenced-by-count": 119,
  "title": "A Cytoplasmic Protein Inhibits the GTPase Activity of H-Ras in a Phospholipid-Dependent Manner",
  "prefix": "10.1126",
  "volume": "250",
  "author": [
    {
      "given": "Men-Hwei",
      "family": "Tsai",
      "sequence": "first",
      "affiliation": [
        {
          "name": "Department of Molecular Biology, The Cleveland Clinic Foundation, Cleveland, OH 44195."
        }
      ]
    },
    {
      "given": "Chun-Li",
      "family": "Yu",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Department of Molecular Biology, The Cleveland Clinic Foundation, Cleveland, OH 44195."
        }
      ]
    },
    {
      "given": "Dennis W.",
      "family": "Stacey",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Department of Molecular Biology, The Cleveland Clinic Foundation, Cleveland, OH 44195."
        }
      ]
    }
  ],
  "member": "221",
  "reference": [
    {
      "key": "e_1_2_1_1_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.2833817"
    },
    {
      "key": "e_1_2_1_2_1",
      "doi-asserted-by": "crossref",
      "first-page": "681",
      "DOI": "10.1016/0092-8674(89)90014-7",
      "volume": "59",
      "year": "1989",
      "unstructured": "BALLESTER, R, GENETIC-ANALYSIS OF MAMMALIAN GAP EXPRESSED IN YEAST, CELL 59: 681 (1989).",
      "journal-title": "CELL"
    },
    {
      "key": "e_1_2_1_3_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1146/annurev.bi.56.070187.004023"
    },
    {
      "key": "e_1_2_1_4_1",
      "doi-asserted-by": "crossref",
      "first-page": "149",
      "DOI": "10.1016/0092-8674(86)90729-4",
      "volume": "46",
      "year": "1986",
      "unstructured": "BRUGGE, J.S., THE P35/P36 SUBSTRATES OF PROTEIN-TYROSINE KINASES AS INHIBITORS OF PHOSPHOLIPASE-A2, CELL 46: 149 (1986).",
      "journal-title": "CELL"
    },
    {
      "key": "e_1_2_1_5_1",
      "doi-asserted-by": "crossref",
      "first-page": "548",
      "DOI": "10.1038/332548a0",
      "volume": "332",
      "year": "1988",
      "unstructured": "CALES, C, THE CYTOPLASMIC PROTEIN GAP IS IMPLICATED AS THE TARGET FOR REGULATION BY THE RAS GENE-PRODUCT, NATURE 332: 548 (1988).",
      "journal-title": "NATURE"
    },
    {
      "key": "e_1_2_1_6_1",
      "doi-asserted-by": "crossref",
      "first-page": "479",
      "DOI": "10.1016/0092-8674(85)90105-9",
      "volume": "42",
      "year": "1985",
      "unstructured": "CARNEY, D.H., PHOSPHOINOSITIDES IN MITOGENESIS - NEOMYCIN INHIBITS THROMBIN-STIMULATED PHOSPHOINOSITIDE TURNOVER AND INITIATION OF CELL-PROLIFERATION, CELL 42: 479 (1985).",
      "journal-title": "CELL"
    },
    {
      "key": "e_1_2_1_7_1",
      "doi-asserted-by": "crossref",
      "first-page": "193",
      "DOI": "10.1146/annurev.bi.48.070179.001205",
      "volume": "48",
      "year": "1979",
      "unstructured": "CARPENTER, G, EPIDERMAL GROWTH-FACTOR, ANNUAL REVIEW OF BIOCHEMISTRY 48: 193 (1979).",
      "journal-title": "ANNUAL REVIEW OF BIOCHEMISTRY"
    },
    {
      "key": "e_1_2_1_8_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/343377a0"
    },
    {
      "key": "e_1_2_1_9_1",
      "doi-asserted-by": "crossref",
      "first-page": "2658",
      "DOI": "10.1016/S0021-9258(18)69117-3",
      "volume": "263",
      "year": "1988",
      "unstructured": "GRILLONE, L.R., VASOPRESSIN INDUCES V1 RECEPTORS TO ACTIVATE PHOSPHATIDYLINOSITOL-SPECIFIC AND PHOSPHATIDYLCHOLINE-SPECIFIC PHOSPHOLIPASE-C AND STIMULATES THE RELEASE OF ARACHIDONIC-ACID BY AT LEAST 2 PATHWAYS IN THE SMOOTH-MUSCLE CELL-LINE, A-10, JOURNAL OF BIOLOGICAL CHEMISTRY 263: 2658 (1988).",
      "journal-title": "JOURNAL OF BIOLOGICAL CHEMISTRY"
    },
    {
      "key": "e_1_2_1_10_1",
      "doi-asserted-by": "crossref",
      "first-page": "2329",
      "DOI": "10.1016/S0021-9258(19)69783-8",
      "volume": "256",
      "year": "1981",
      "unstructured": "HABENICHT, AJR, EARLY CHANGES IN PHOSPHATIDYLINOSITOL AND ARACHIDONIC-ACID METABOLISM IN QUIESCENT SWISS 3T3 CELLS STIMULATED TO DIVIDE BY PLATELET-DERIVED GROWTH-FACTOR, JOURNAL OF BIOLOGICAL CHEMISTRY 256: 2329 (1981).",
      "journal-title": "JOURNAL OF BIOLOGICAL CHEMISTRY"
    },
    {
      "key": "e_1_2_1_11_1",
      "doi-asserted-by": "crossref",
      "first-page": "396",
      "DOI": "10.1016/0005-2760(88)90225-1",
      "volume": "958",
      "year": "1988",
      "unstructured": "LAHOUA, Z, SERUM-INDUCED ARACHIDONIC-ACID RELEASE AND PROSTAGLANDIN BIOSYNTHESIS ARE POTENTIATED BY OXYGENATED STEROLS IN NRK 49F CELLS, BIOCHIMICA ET BIOPHYSICA ACTA 958: 396 (1988).",
      "journal-title": "BIOCHIMICA ET BIOPHYSICA ACTA"
    },
    {
      "key": "e_1_2_1_12_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0092-8674(89)90047-0"
    },
    {
      "key": "e_1_2_1_13_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0092-8674(89)90048-2"
    },
    {
      "key": "e_1_2_1_14_1",
      "doi-asserted-by": "crossref",
      "first-page": "241",
      "DOI": "10.1038/313241a0",
      "volume": "313",
      "year": "1985",
      "unstructured": "MULCAHY, L.S., REQUIREMENT FOR RAS PROTO-ONCOGENE FUNCTION DURING SERUM-STIMULATED GROWTH OF NIH-3T3-CELLS, NATURE 313: 241 (1985).",
      "journal-title": "NATURE"
    },
    {
      "key": "e_1_2_1_15_1",
      "doi-asserted-by": "crossref",
      "first-page": "3584",
      "DOI": "10.1016/S0021-9258(19)83662-1",
      "volume": "260",
      "year": "1985",
      "unstructured": "NAKAMURA, T, SIMULTANEOUS INHIBITIONS OF INOSITOL PHOSPHOLIPID BREAKDOWN, ARACHIDONIC-ACID RELEASE, AND HISTAMINE-SECRETION IN MAST-CELLS BY ISLET-ACTIVATING PROTEIN, PERTUSSIS TOXIN - A POSSIBLE INVOLVEMENT OF THE TOXIN-SPECIFIC SUBSTRATE IN THE CA-2+-MOBILIZING RECEPTOR-MEDIATED BIOSIGNALING SYSTEM, JOURNAL OF BIOLOGICAL CHEMISTRY 260: 3584 (1985).",
      "journal-title": "JOURNAL OF BIOLOGICAL CHEMISTRY"
    },
    {
      "key": "e_1_2_1_16_1",
      "doi-asserted-by": "crossref",
      "first-page": "6280",
      "DOI": "10.1021/bi00524a057",
      "volume": "20",
      "year": "1981",
      "unstructured": "SAWYER, S.T., ENHANCEMENT OF CALCIUM-UPTAKE AND PHOSPHATIDYLINOSITOL TURNOVER BY EPIDERMAL GROWTH-FACTOR IN A-431 CELLS, BIOCHEMISTRY 20: 6280 (1981).",
      "journal-title": "BIOCHEMISTRY"
    },
    {
      "key": "e_1_2_1_17_1",
      "doi-asserted-by": "crossref",
      "first-page": "540",
      "DOI": "10.1038/320540a0",
      "volume": "320",
      "year": "1986",
      "unstructured": "SMITH, M.R., REQUIREMENT FOR C-RAS PROTEINS DURING VIRAL ONCOGENE TRANSFORMATION, NATURE 320: 540 (1986).",
      "journal-title": "NATURE"
    },
    {
      "key": "e_1_2_1_18_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.2821624"
    },
    {
      "key": "e_1_2_1_19_1",
      "doi-asserted-by": "crossref",
      "first-page": "522",
      "DOI": "10.1126/science.2536192",
      "volume": "243",
      "year": "1989",
      "unstructured": "TSAI, M.H., THE EFFECT OF GTPASE ACTIVATING PROTEIN UPON RAS IS INHIBITED BY MITOGENICALLY RESPONSIVE LIPIDS, SCIENCE 243: 522 (1989).",
      "journal-title": "SCIENCE"
    },
    {
      "key": "e_1_2_1_20_1",
      "unstructured": "TSAI M.H. unpublished data."
    },
    {
      "key": "e_1_2_1_21_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/335090a0"
    },
    {
      "key": "e_1_2_1_22_1",
      "doi-asserted-by": "crossref",
      "first-page": "63",
      "DOI": "10.1016/0092-8674(88)90531-4",
      "volume": "52",
      "year": "1988",
      "unstructured": "YU, C.L., CELLULAR RAS ACTIVITY AND PHOSPHOLIPID-METABOLISM, CELL 52: 63 (1988).",
      "journal-title": "CELL"
    }
  ],
  "container-title": "Science",
  "original-title": [],
  "language": "en",
  "link": [
    {
      "URL": "https://www.science.org/doi/pdf/10.1126/science.2237442",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "similarity-checking"
    }
  ],
  "deposited": {
    "date-parts": [
      [
        2024,
        1,
        12
      ]
    ],
    "date-time": "2024-01-12T09:51:55Z",
    "timestamp": 1705053115000
  },
  "score": 1,
  "resource": {
    "primary": {
      "URL": "https://www.science.org/doi/10.1126/science.2237442"
    }
  },
  "subtitle": [],
  "short-title": [],
  "issued": {
    "date-parts": [
      [
        1990,
        11,
        16
      ]
    ]
  },
  "references-count": 22,
  "journal-issue": {
    "issue": "4983",
    "published-print": {
      "date-parts": [
        [
          1990,
          11,
          16
        ]
      ]
    }
  },
  "alternative-id": [
    "10.1126/science.2237442"
  ],
  "URL": "http://dx.doi.org/10.1126/science.2237442",
  "relation": {},
  "ISSN": [
    "0036-8075",
    "1095-9203"
  ],
  "subject": [],
  "container-title-short": "Science",
  "published": {
    "date-parts": [
      [
        1990,
        11,
        16
      ]
    ]
  }
}