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

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

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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.

Original languageEnglish (US)
Pages (from-to)8105-8113
Number of pages9
JournalOncogene
Volume21
Issue number53
DOIs
StatePublished - Nov 21 2002

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Type C Phospholipases
Intercellular Signaling Peptides and Proteins
Platelet-Derived Growth Factor
Phosphoinositide Phospholipase C
Guanine Nucleotide Exchange Factors
Platelet-Derived Growth Factor Receptors
Monomeric GTP-Binding Proteins
Apoptosis
Growth

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Song, C., Satoh, T., Edamatsu, H., Wu, D., Tadano, M., Gao, X., & Kataoka, T. (2002). Differential roles of Ras and Rap1 in growth factor-dependent activation of phospholipase Cε. Oncogene, 21(53), 8105-8113. https://doi.org/10.1038/sj.onc.1206003
Song, Chunhua ; Satoh, Takaya ; Edamatsu, Hironori ; Wu, Dongmei ; Tadano, Makoto ; Gao, Xianlong ; Kataoka, Tohru. / Differential roles of Ras and Rap1 in growth factor-dependent activation of phospholipase Cε. In: Oncogene. 2002 ; Vol. 21, No. 53. pp. 8105-8113.
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Song, C, Satoh, T, Edamatsu, H, Wu, D, Tadano, M, Gao, X & Kataoka, T 2002, 'Differential roles of Ras and Rap1 in growth factor-dependent activation of phospholipase Cε', Oncogene, vol. 21, no. 53, pp. 8105-8113. https://doi.org/10.1038/sj.onc.1206003

Differential roles of Ras and Rap1 in growth factor-dependent activation of phospholipase Cε. / Song, Chunhua; Satoh, Takaya; Edamatsu, Hironori; Wu, Dongmei; Tadano, Makoto; Gao, Xianlong; Kataoka, Tohru.

In: Oncogene, Vol. 21, No. 53, 21.11.2002, p. 8105-8113.

Research output: Contribution to journalArticle

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AU - Song, Chunhua

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