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Palmitoylation and Phosphorylation of the Na + ‐H + Exchanger Isoform 1 (NHE1) Regulate of Cell Proliferation and Stress Fiber Formation: PI3 Kinase and AKT Signaling
Author(s) -
Kahlstorf Grant,
Wallert Mark
Publication year - 2021
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.2021.35.s1.04038
Subject(s) - palmitoylation , microbiology and biotechnology , protein kinase b , phosphorylation , stress fiber , kinase , sodium–hydrogen antiporter , chemistry , pi3k/akt/mtor pathway , signal transduction , biology , biochemistry , focal adhesion , enzyme , organic chemistry , sodium , cysteine
The Na + ‐H + Exchanger Isoform 1 (NHE1) is a 12‐pass transmembrane transport protein that exchanges one extracellular Na + for one intracellular H + with the primary function of intracellular pH regulation. Through the pH regulation NHE1 contributes to the regulation of cell proliferation and stress fiber formation. The regulation of NHE1 is extremely complex and involves protein and lipid binding sites including phosphorylation and palmitoylation sites. NHE1 transport activity is regulated by a series of signaling pathways which include kinases of the PI3 Kinase / AKT signaling pathways. Recently it was demonstrated that inhibition of either PI3 Kinase or AKT lead to an increase in the palmitoylation of NHE1. Here we assess the role of this interaction between palmitoylation and phosphorylation in the regulation of cell proliferation and stress fiber formation in PSN cells. It is hypothesized that inhibiting phosphorylation, palmitoylation, or both will differentially regulate cell proliferation and stress fiber formation in these cells. PSN cells are Chinese hamster lung fibroblast that stably express human NHE1. We evaluated cell proliferation and stress fiber formation in the presence and absence of combinations of inhibitors that alter NHE1 regulation and transport activity including, LY294002 (PI3 Kinase), MK 2206 (AKT), 2‐Bromopalmitate (Palmitoylation), and Ethylisopropylamiloride (NHE1).