DOI: 10.1016/s0014-5793(97)01252-0. Ro31‐8220 inhibits protein kinase C to block the phorbol ester‐stimulated release of choline‐ and ethanolamine‐metabolites from C6 glioma cells: p70 S6 kinase and MAPKAP kinase‐1β do not function downstream of PKC in activating PLD

Ro31‐8220 inhibits protein kinase C to block the phorbol ester‐stimulated release of choline‐ and ethanolamine‐metabolites from C6 glioma cells: p70 S6 kinase and MAPKAP kinase‐1β do not function downstream of PKC in activating PLD

10.1016/s0014-5793(97)01252-0

Crossref journal-article

Wiley

FEBS Letters (311)

Abstract

The use of bisindolylmaleimide derivatives of staurosporine as selective inhibitors of protein kinase C (PKC) is in doubt following the report by Alessi [FEBS Lett. 402 (1997) 121–123] that Ro31‐8220 and GF109203X are potent in vitro inhibitors of p70 S6 kinase and mitogen‐activated protein kinase‐activated protein kinase‐1β, as well as of PKC. Here we show that the phorbol ester‐stimulated release of choline‐ and ethanolamine‐metabolites from C6 glioma cells due to phospholipid hydrolysis by phospholipase D (PLD) is not inhibited by rapamycin or PD98059, specific inhibitors respectively of p70 S6 kinase and MAPKK (MEK) and thus of MAPKAP kinase‐1β but is still completely blocked by Ro31‐8220. We conclude therefore that p70S6k and MAPKAP kinase‐1β as well as MAPK are not involved in signalling pathways downstream of PKC that regulate phorbol ester‐stimulated phospholipid turnover and that the inhibitory action of Ro31‐8220 occurs by blocking PKC which regulates at least one pathway to PLD activation. The PI‐3 kinase inhibitor, wortmannin, inhibits the phorbol ester‐stimulated release of ethanolamine‐ but not choline‐metabolites from C6 cells suggesting that different PLD isoforms regulate the turnover of PtdEth and PtdCho in C6 cells. Both PLD isoforms are activated via PKC but the PtdEth‐PLD is also regulated via a wortmannin‐sensitive pathway.

Bibliography

Morreale, A., Mallon, B., Beale, G., Watson, J., & Rumsby, M. (1997). Ro31â8220 inhibits protein kinase C to block the phorbol esterâstimulated release of cholineâ and ethanolamineâmetabolites from C6 glioma cells: p70 S6 kinase and MAPKAP kinaseâ1Î² do not function downstream of PKC in activating PLD. FEBS Letters, 417(1), 38â42. Portico.

Authors 5

Angela Morreale (first)
Barbara Mallon (additional)
Gary Beale (additional)
John Watson (additional)
Martin Rumsby (additional)

References 29 Referenced 13

Dates

Type	When
Created	23 years, 1 month ago (July 25, 2002, 1:53 p.m.)
Deposited	1 year, 11 months ago (Sept. 16, 2023, 12:15 p.m.)
Indexed	1 year, 3 months ago (May 31, 2024, 12:32 p.m.)
Issued	27 years, 10 months ago (Nov. 3, 1997)
Published	27 years, 10 months ago (Nov. 3, 1997)
Published Online	27 years, 9 months ago (Nov. 25, 1997)
Published Print	27 years, 10 months ago (Nov. 3, 1997)

Funders 0

None

BibTeX

@article{Morreale_1997, title={Ro31‐8220 inhibits protein kinase C to block the phorbol ester‐stimulated release of choline‐ and ethanolamine‐metabolites from C6 glioma cells: p70 S6 kinase and MAPKAP kinase‐1β do not function downstream of PKC in activating PLD}, volume={417}, ISSN={1873-3468}, url={http://dx.doi.org/10.1016/s0014-5793(97)01252-0}, DOI={10.1016/s0014-5793(97)01252-0}, number={1}, journal={FEBS Letters}, publisher={Wiley}, author={Morreale, Angela and Mallon, Barbara and Beale, Gary and Watson, John and Rumsby, Martin}, year={1997}, month=nov, pages={38–42} }

JSON

{
  "indexed": {
    "date-parts": [
      [
        2024,
        5,
        31
      ]
    ],
    "date-time": "2024-05-31T16:32:25Z",
    "timestamp": 1717173145960
  },
  "reference-count": 29,
  "publisher": "Wiley",
  "issue": "1",
  "license": [
    {
      "start": {
        "date-parts": [
          [
            1997,
            11,
            25
          ]
        ],
        "date-time": "1997-11-25T00:00:00Z",
        "timestamp": 880416000000
      },
      "content-version": "vor",
      "delay-in-days": 22,
      "URL": "http://onlinelibrary.wiley.com/termsAndConditions#vor"
    }
  ],
  "content-domain": {
    "domain": [],
    "crossmark-restriction": false
  },
  "published-print": {
    "date-parts": [
      [
        1997,
        11,
        3
      ]
    ]
  },
  "abstract": "<jats:p>The use of bisindolylmaleimide derivatives of staurosporine as selective inhibitors of protein kinase C (PKC) is in doubt following the report by Alessi [FEBS Lett. 402 (1997) 121\u2013123] that Ro31\u20108220 and GF109203X are potent in vitro inhibitors of p70 S6 kinase and mitogen\u2010activated protein kinase\u2010activated protein kinase\u20101\u03b2, as well as of PKC. Here we show that the phorbol ester\u2010stimulated release of choline\u2010 and ethanolamine\u2010metabolites from C6 glioma cells due to phospholipid hydrolysis by phospholipase D (PLD) is not inhibited by rapamycin or PD98059, specific inhibitors respectively of p70 S6 kinase and MAPKK (MEK) and thus of MAPKAP kinase\u20101\u03b2 but is still completely blocked by Ro31\u20108220. We conclude therefore that p70<jats:sup>S6k</jats:sup> and MAPKAP kinase\u20101\u03b2 as well as MAPK are not involved in signalling pathways downstream of PKC that regulate phorbol ester\u2010stimulated phospholipid turnover and that the inhibitory action of Ro31\u20108220 occurs by blocking PKC which regulates at least one pathway to PLD activation. The PI\u20103 kinase inhibitor, wortmannin, inhibits the phorbol ester\u2010stimulated release of ethanolamine\u2010 but not choline\u2010metabolites from C6 cells suggesting that different PLD isoforms regulate the turnover of PtdEth and PtdCho in C6 cells. Both PLD isoforms are activated via PKC but the PtdEth\u2010PLD is also regulated via a wortmannin\u2010sensitive pathway.</jats:p>",
  "DOI": "10.1016/s0014-5793(97)01252-0",
  "type": "journal-article",
  "created": {
    "date-parts": [
      [
        2002,
        7,
        25
      ]
    ],
    "date-time": "2002-07-25T17:53:27Z",
    "timestamp": 1027619607000
  },
  "page": "38-42",
  "source": "Crossref",
  "is-referenced-by-count": 13,
  "title": "Ro31\u20108220 inhibits protein kinase C to block the phorbol ester\u2010stimulated release of choline\u2010 and ethanolamine\u2010metabolites from C6 glioma cells: p70 S6 kinase and MAPKAP kinase\u20101\u03b2 do not function downstream of PKC in activating PLD",
  "prefix": "10.1002",
  "volume": "417",
  "author": [
    {
      "given": "Angela",
      "family": "Morreale",
      "sequence": "first",
      "affiliation": []
    },
    {
      "given": "Barbara",
      "family": "Mallon",
      "sequence": "additional",
      "affiliation": []
    },
    {
      "given": "Gary",
      "family": "Beale",
      "sequence": "additional",
      "affiliation": []
    },
    {
      "given": "John",
      "family": "Watson",
      "sequence": "additional",
      "affiliation": []
    },
    {
      "given": "Martin",
      "family": "Rumsby",
      "sequence": "additional",
      "affiliation": []
    }
  ],
  "member": "311",
  "published-online": {
    "date-parts": [
      [
        1997,
        11,
        25
      ]
    ]
  },
  "reference": [
    {
      "key": "e_1_2_6_2_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0898-6568(94)90020-5"
    },
    {
      "key": "e_1_2_6_3_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0014-5793(89)81494-2"
    },
    {
      "key": "e_1_2_6_4_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1042/bj2940335"
    },
    {
      "key": "e_1_2_6_5_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1042/bj3060115"
    },
    {
      "key": "e_1_2_6_6_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1042/bj3131039"
    },
    {
      "key": "e_1_2_6_7_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0014-5793(96)01510-4"
    },
    {
      "key": "e_1_2_6_8_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1042/bst021354s"
    },
    {
      "key": "e_1_2_6_9_1",
      "unstructured": "Mallon B.S. (1996) D.Phil. thesis University of York."
    },
    {
      "key": "e_1_2_6_10_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1042/bj2810597"
    },
    {
      "key": "e_1_2_6_11_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0304-3940(92)90547-K"
    },
    {
      "key": "e_1_2_6_12_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.270.46.27489"
    },
    {
      "key": "e_1_2_6_13_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0009-3084(96)02547-9"
    },
    {
      "key": "e_1_2_6_14_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0005-2760(94)90186-4"
    },
    {
      "key": "e_1_2_6_15_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0952-7915(93)90090-F"
    },
    {
      "key": "e_1_2_6_16_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0165-6147(96)10016-X"
    },
    {
      "key": "e_1_2_6_17_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1139/o96-050"
    },
    {
      "key": "e_1_2_6_18_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0014-5793(97)00444-4"
    },
    {
      "key": "e_1_2_6_19_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0929-7855(96)00552-4"
    },
    {
      "key": "e_1_2_6_20_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0005-2760(89)90075-1"
    },
    {
      "key": "e_1_2_6_21_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.271.43.27018"
    },
    {
      "key": "e_1_2_6_22_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0014-5793(94)80490-7"
    },
    {
      "key": "e_1_2_6_23_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.88.2.598"
    },
    {
      "key": "e_1_2_6_24_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.270.25.14935"
    },
    {
      "key": "e_1_2_6_25_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0021-9258(18)98557-1"
    },
    {
      "key": "e_1_2_6_26_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1042/bj3131039"
    },
    {
      "key": "e_1_2_6_27_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0014-5793(93)81127-L"
    },
    {
      "key": "e_1_2_6_28_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1152/physrev.1997.77.2.303"
    },
    {
      "key": "e_1_2_6_29_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.1380182"
    },
    {
      "key": "e_1_2_6_30_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0092-8674(92)90643-Q"
    }
  ],
  "container-title": "FEBS Letters",
  "original-title": [],
  "language": "en",
  "link": [
    {
      "URL": "https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1016%2FS0014-5793%2897%2901252-0",
      "content-type": "application/pdf",
      "content-version": "vor",
      "intended-application": "text-mining"
    },
    {
      "URL": "https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1016%2FS0014-5793(97)01252-0",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "text-mining"
    },
    {
      "URL": "https://febs.onlinelibrary.wiley.com/doi/pdf/10.1016/S0014-5793%2897%2901252-0",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "similarity-checking"
    }
  ],
  "deposited": {
    "date-parts": [
      [
        2023,
        9,
        16
      ]
    ],
    "date-time": "2023-09-16T16:15:10Z",
    "timestamp": 1694880910000
  },
  "score": 1,
  "resource": {
    "primary": {
      "URL": "https://febs.onlinelibrary.wiley.com/doi/10.1016/S0014-5793%2897%2901252-0"
    }
  },
  "subtitle": [],
  "short-title": [],
  "issued": {
    "date-parts": [
      [
        1997,
        11,
        3
      ]
    ]
  },
  "references-count": 29,
  "journal-issue": {
    "issue": "1",
    "published-print": {
      "date-parts": [
        [
          1997,
          11,
          3
        ]
      ]
    }
  },
  "alternative-id": [
    "10.1016/S0014-5793(97)01252-0"
  ],
  "URL": "http://dx.doi.org/10.1016/S0014-5793(97)01252-0",
  "relation": {},
  "ISSN": [
    "0014-5793",
    "1873-3468"
  ],
  "subject": [],
  "container-title-short": "FEBS Letters",
  "published": {
    "date-parts": [
      [
        1997,
        11,
        3
      ]
    ]
  }
}