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β 1 Pix suppresses the activity of the epithelial Na + channel through 14‐3‐3 binding
Author(s) -
Pavlov Tengis S,
Chahdi Ahmed,
Sorokin Andrey,
Staruschenko Alexander
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.998.9
Subject(s) - epithelial sodium channel , rac1 , cdc42 , guanine nucleotide exchange factor , amiloride , chemistry , microbiology and biotechnology , mutant , gtpase , biology , biochemistry , sodium , signal transduction , gene , organic chemistry
β 1 Pix has been identified as a p21‐activated kinase (Pak)‐interacting exchange factor and serves as a guanine nucleotide exchange factor (GEF) for Rac1 and Cdc42. Furthermore, it was shown that βPix can bind 14‐3‐3 proteins and act as a scaffolding protein. We demonstrate here that βPix is highly expressed in immortalized mouse collecting duct mpkCCD c14 cells. Additionally we have shown that β 1 Pix expression markedly decrease ENaC activity. Coexpression of β 1 Pix with ENaC decreased amiloride‐sensitive current density in CHO cells from 365 ± 35 to 158 ± 29 pA/pF. This effect did not occur through GEF activity of β 1 Pix because coexpression of Rac1 with ENaC markedly increased channel activity and coexpression of wild type and constitutively active (G12V) Cdc42 had no effect on ENaC activity. Moreover Δ602‐611 β 1 Pix construct which did not bind 14‐3‐3 but retained GEF activity had no effect on ENaC activity. In contrast, β 1 Pix (L238R,L239R) mutant which has no GEF activity decreased current density to the similar extent as wild type β 1 Pix. Thus, we can conclude that ß1Pix decreases ENaC activity via 14‐3‐3 recruitment but not through GEF activity. Supported by NIH, AHA and ASN.