Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Paper
  • Published:

Differential roles of Ras and Rap1 in growth factor-dependent activation of phospholipase Cε

Oncogene volume 21, pages 8105–8113 (2002)Cite this article

Abstract

Phospholipase Cε is a phosphoinositide-specific phospholipase C that selectively associates with Ras and Rap small GTPases as a target. Here we explored the molecular basis of the Rap1- as well as Ras-mediated regulation of phospholipase Cε upon platelet-derived growth factor stimulation by using a receptor mutant deficient in its ability to phosphorylate and activate phospholipase Cγ. Following platelet-derived growth factor treatment, this receptor induces persistent activation of ectopically expressed PLCε through activation of Ras and Rap1. The rapid and initial phase of the activation is mediated by Ras, whereas Rap1 is responsible for the prolonged activation. We further demonstrate that the CDC25 homology domain, which exhibits guanine nucleotide exchange factor activity toward Rap1, but not Ras, is critical for the prolonged activation of phospholipase Cε. Platelet-derived growth factor prevented the hematopoietic BaF3 cells containing the mutant receptor from undergoing apoptosis, and enabled these cells to proliferate, only when phospholipase Cε was expressed. Therefore, the phospholipase C signal is suggested to be critical for survival and growth of BaF3 cells.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6

Similar content being viewed by others

References

  • Baron CL, Malhotra V . 2002 Science 295: 325–328

  • Beranger F, Goud B, Tavitian A, de Gunzburg J . 1991 Proc. Natl. Acad. Sci. USA 88: 1606–1610

  • Bos JL . 1998 EMBO J. 17: 6776–6782

  • Bos JL, de Rooij J, Reedquist KA . 2001 Nat. Rev. Mol. Cell Biol. 2: 369–377

  • De Matteis MA, Santini G, Kahn RA, Tullio GD, Luini A . 1993 Nature 364: 818–821

  • Evellin S, Nolte J, Tysack K, vom Dorp F, Thiel M, Oude Weernink PA, Jakobs KH, Webb E, Lomasney JW, Schmidt M . 2002 J. Biol. Chem. 277: 16805–16813

  • Fantl WJ, Johnson DE, Williams LT . 1993 Annu. Rev. Biochem. 62: 453–481

  • Gao X, Satoh T, Liao Y, Song C, Hu C-D, Kariya K, Kataoka T . 2001 J. Biol. Chem. 276: 42219–42225

  • Jin TG, Satoh T, Liao Y, Song C, Gao X, Kariya K, Hu C-D, Kataoka T . 2001 J. Biol. Chem. 276: 30301–30307

  • Johnson DE . 1998 Front. Biosci. 3: d313–d324

  • Katagiri K, Hattori M, Minato N, Irie S, Takatsu K, Kinashi T . 2000 Mol. Cell. Biol. 20: 1956–1969

  • Kelley GG, Reks SE, Ondrako JM, Smrcka AV . 2001 EMBO J. 20: 743–754

  • Kurachi H, Wada Y, Tsukamoto N, Maeda M, Kubota H, Hattori M, Iwai K, Minato N . 1997 J. Biol. Chem. 272: 28081–28088

  • Lopez I, Mak EC, Ding J, Hamm HE, Lomasney JW . 2001 J. Biol. Chem. 276: 2758–2765

  • Matsubara K, Kishida S, Matsuura Y, Kitayama H, Noda M, Kikuchi A . 1999 Oncogene 18: 1303–1312

  • Mizushima S, Nagata S . 1990 Nucleic Acids Res. 18: 5322

  • Ohba Y, Mochizuki N, Matsuo K, Yamashita S, Nakaya M, Hashimoto Y, Hamaguchi M, Kurata T, Nagashima K, Matsuda M . 2000 Mol. Cell. Biol. 20: 6074–6083

  • Reedquist KA, Ross E, Koop EA, Wolthuis RM, Zwartkruis FJ, van Kooyk Y, Salmon M, Buckley CD, Bos JL . 2000 J. Cell Biol. 148: 1151–1158

  • Satoh T, Fantl WJ, Escobedo JA, Williams LT, Kaziro Y . 1993 Mol. Cell. Biol. 13: 3706–3713

  • Schmidt A, Caron E, Hall A . 2001a Mol. Cell. Biol. 21: 438–448

  • Schmidt M, Evellin S, Oude Weernink PA, vom Dorp F, Rehmann H, Lomasney JW, Jakobs KH . 2001b Nat. Cell Biol. 3: 1020–1024

  • Shibatohge M, Kariya K, Liao Y, Hu C-D, Watari Y, Goshima M, Shima F, Kataoka T . 1998 J. Biol. Chem. 273: 6218–6222

  • Shima F, Yamawaki-Kataoka Y, Yanagihara C, Tamada M, Okada T, Kariya K, Kataoka T . 1997 Mol. Cell. Biol. 17: 1057–1064

  • Singer WD, Brown HA, Sternweis PC . 1997 Annu. Rev. Biochem. 66: 475–509

  • Song C, Hu C-D, Masago M, Kariya K, Yamawaki-Kataoka Y, Shibatohge M, Wu D, Satoh T, Kataoka T . 2001 J. Biol. Chem. 276: 2752–2757

  • Tsukamoto N, Hattori M, Yang H, Bos JL, Minato N . 1999 J. Biol. Chem. 274: 18463–18469

  • Wienecke R, Maize JC, Shoarinejad F, Vass WC, Reed J, Bonifacino JS, Resau JH, de Gunzburg J, Yeung RS, DeClue JE . 1996 Oncogene 13: 913–923

  • Wing MR, Houston D, Kelley GG, Der CJ, Siderovski DP, Harden TK . 2001 J. Biol. Chem. 276: 48257–48261

  • York RD, Molliver DC, Grewal SS, Stenberg PE, McCleskey EW, Stork PJ . 2000 Mol. Cell. Biol. 20: 8069–8083

  • York RD, Yao H, Dillon T, Ellig CL, Eckert SP, McCleskey EW, Stork PJ . 1998 Nature 392: 622–626

Download references

Acknowledgements

We thank Dr Nagahiro Minato for the SPA-1 cDNA and Dr Garry Nolan for helpful advice. This investigation was supported by Grants-in-aid for Scientific Research in Priority Areas and for Scientific Research (B) and (C) from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

Author information

Authors and Affiliations

  1. Division of Molecular Biology, Department of Molecular and Cellular Biology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, 650-0017, Kobe, Japan

    Chunhua Song, Takaya Satoh, Hironori Edamatsu, Dongmei Wu, Makoto Tadano, Xianlong Gao & Tohru Kataoka

Authors
  1. Chunhua Song
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Takaya Satoh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hironori Edamatsu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Dongmei Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Makoto Tadano
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Xianlong Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Tohru Kataoka
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Tohru Kataoka.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Song, C., Satoh, T., Edamatsu, H. et al. Differential roles of Ras and Rap1 in growth factor-dependent activation of phospholipase Cε. Oncogene 21, 8105–8113 (2002). https://doi.org/10.1038/sj.onc.1206003

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1206003

Keywords

This article is cited by

Search

Advanced search

Quick links