H-Ras mediates the inhibitory effect of epidermal growth factor on the epithelial Na+ channel

PloS One
Il-Ha LeeAnuwat Dinudom

Abstract

The present study investigates the role of small G-proteins of the Ras family in the epidermal growth factor (EGF)-activated cellular signalling pathway that downregulates activity of the epithelial Na+ channel (ENaC). We found that H-Ras is a key component of this EGF-activated cellular signalling mechanism in M1 mouse collecting duct cells. Expression of a constitutively active H-Ras mutant inhibited the amiloride-sensitive current. The H-Ras-mediated signalling pathway that inhibits activity of ENaC involves c-Raf, and that the inhibitory effect of H-Ras on ENaC is abolished by the MEK1/2 inhibitor, PD98059. The inhibitory effect of H-Ras is not mediated by Nedd4-2, a ubiquitin protein ligase that regulates the abundance of ENaC at the cell surface membrane, or by a negative effect of H-Ras on proteolytic activation of the channel. The inhibitory effects of EGF and H-Ras on ENaC, however, were not observed in cells in which expression of caveolin-1 (Cav-1) had been knocked down by siRNA. These findings suggest that the inhibitory effect of EGF on ENaC-dependent Na+ absorption is mediated via the H-Ras/c-Raf, MEK/ERK signalling pathway, and that Cav-1 is an essential component of this EGF-activated signalling mechanism. Taken...Continue Reading

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Citations

May 29, 2020·American Journal of Physiology. Renal Physiology·Shan ChenHui Cai
Aug 28, 2019·International Journal of Molecular Sciences·Giovanna CapolongoMiriam Zacchia
Mar 25, 2016·American Journal of Physiology. Cell Physiology·Lili XuXinfeng Liu
Dec 11, 2020·Stem Cell Research & Therapy·Janine ObendorfMandy Laube

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BETA
GTPases
Transfection
electrophoresis

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