Role of Rac GTPase in the nuclear signaling by EGF

Byung Chul Kim; Jae Hong Kim

doi:10.1016/S0014-5793(97)00289-5

Role of Rac GTPase in the nuclear signaling by EGF

Byung Chul Kim, Jae Hong Kim

Research output: Contribution to journal › Article › peer-review

17 Citations (Scopus)

Abstract

The role of Rac in epidermal growth factor (EGF)-induced c-fos serum response element (SRE) activation was examined in Rat-2 fibroblast cells. By reporter gene analysis following transient or stable transfections, with pEXV-RacN17 encoding a dominant-negative mutant of Rac, EGF-induced activation of c-fos SRE-luciferase gene was shown to be selectively inhibited, suggesting that Rac activity is necessary for the full activation of SRE by EGF. Our further study to analyze the downstream mediator of Rac in EGF-signaling cascade demonstrated that there is a functional link between Rac and phospholipase A₂ (PLA₂) activation and further that PLA₂ mediates, at least partly, the Rac signaling to SRF. Together, our results point to a critical role of Rac and Rac-activated PLA₂ in the EGF-signaling cascade to c-fos SRE. We propose that 'Rac-PLA₂' cascade is one of the major signaling pathways by which EGF stimulates c-fos SRE.

Original language	English
Pages (from-to)	7-12
Number of pages	6
Journal	FEBS Letters
Volume	407
Issue number	1
DOIs	https://doi.org/10.1016/S0014-5793(97)00289-5
Publication status	Published - 1997 Apr 21
Externally published	Yes

Bibliographical note

Funding Information:
This study was supported by NON-DIRECTED RESEARCH FUND, Korea Research Foundation, 1996 (to J.H. Kim). We wish to thank Dr. Allan Hall (University College, London, UK) and Dr. D.S. Na (Ulsan Medical School, Seoul, Korea) for providing us pEXV-RacN17 and pcDNA3-LC1 plasmid, respectively.

Keywords

C-fos
Epidermal growth factor
Phospholipase A
Rac GTPase
Serum response element
Signal transduction

ASJC Scopus subject areas

Biophysics
Structural Biology
Biochemistry
Molecular Biology
Genetics
Cell Biology

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title = "Role of Rac GTPase in the nuclear signaling by EGF",

abstract = "The role of Rac in epidermal growth factor (EGF)-induced c-fos serum response element (SRE) activation was examined in Rat-2 fibroblast cells. By reporter gene analysis following transient or stable transfections, with pEXV-RacN17 encoding a dominant-negative mutant of Rac, EGF-induced activation of c-fos SRE-luciferase gene was shown to be selectively inhibited, suggesting that Rac activity is necessary for the full activation of SRE by EGF. Our further study to analyze the downstream mediator of Rac in EGF-signaling cascade demonstrated that there is a functional link between Rac and phospholipase A2 (PLA2) activation and further that PLA2 mediates, at least partly, the Rac signaling to SRF. Together, our results point to a critical role of Rac and Rac-activated PLA2 in the EGF-signaling cascade to c-fos SRE. We propose that 'Rac-PLA2' cascade is one of the major signaling pathways by which EGF stimulates c-fos SRE.",

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author = "Kim, {Byung Chul} and Kim, {Jae Hong}",

note = "Funding Information: This study was supported by NON-DIRECTED RESEARCH FUND, Korea Research Foundation, 1996 (to J.H. Kim). We wish to thank Dr. Allan Hall (University College, London, UK) and Dr. D.S. Na (Ulsan Medical School, Seoul, Korea) for providing us pEXV-RacN17 and pcDNA3-LC1 plasmid, respectively.",

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N2 - The role of Rac in epidermal growth factor (EGF)-induced c-fos serum response element (SRE) activation was examined in Rat-2 fibroblast cells. By reporter gene analysis following transient or stable transfections, with pEXV-RacN17 encoding a dominant-negative mutant of Rac, EGF-induced activation of c-fos SRE-luciferase gene was shown to be selectively inhibited, suggesting that Rac activity is necessary for the full activation of SRE by EGF. Our further study to analyze the downstream mediator of Rac in EGF-signaling cascade demonstrated that there is a functional link between Rac and phospholipase A2 (PLA2) activation and further that PLA2 mediates, at least partly, the Rac signaling to SRF. Together, our results point to a critical role of Rac and Rac-activated PLA2 in the EGF-signaling cascade to c-fos SRE. We propose that 'Rac-PLA2' cascade is one of the major signaling pathways by which EGF stimulates c-fos SRE.

AB - The role of Rac in epidermal growth factor (EGF)-induced c-fos serum response element (SRE) activation was examined in Rat-2 fibroblast cells. By reporter gene analysis following transient or stable transfections, with pEXV-RacN17 encoding a dominant-negative mutant of Rac, EGF-induced activation of c-fos SRE-luciferase gene was shown to be selectively inhibited, suggesting that Rac activity is necessary for the full activation of SRE by EGF. Our further study to analyze the downstream mediator of Rac in EGF-signaling cascade demonstrated that there is a functional link between Rac and phospholipase A2 (PLA2) activation and further that PLA2 mediates, at least partly, the Rac signaling to SRF. Together, our results point to a critical role of Rac and Rac-activated PLA2 in the EGF-signaling cascade to c-fos SRE. We propose that 'Rac-PLA2' cascade is one of the major signaling pathways by which EGF stimulates c-fos SRE.

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KW - Epidermal growth factor

KW - Phospholipase A

KW - Rac GTPase

KW - Serum response element

KW - Signal transduction

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Role of Rac GTPase in the nuclear signaling by EGF

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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