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Arachidonic acid induces c‐ Src‐, EGFR‐, and p38 kinase‐ dependent Akt activation in renal proximal tubular cells
Author(s) -
Alexander Larry D
Publication year - 2007
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.21.6.a1334
Subject(s) - protein kinase b , proto oncogene tyrosine protein kinase src , arachidonic acid , chemistry , cancer research , kinase , microbiology and biotechnology , biology , biochemistry , signal transduction , enzyme
Recent studies by our laboratory demonstrate that arachidonic acid activates ERK through c‐Src dependent transactivation of the epidermal growth factor receptor (EGFR) in rabbit proximal tubular epithelial cells. We demonstrate here that stimulation with arachidonic acid results in a time‐ and dose‐dependent activation of Akt which was significantly inhibited by PI3‐ kinase and Akt inhibitors, whereas arachidonic acid‐ induced activation of c‐Src, EGFR, ERK, and p38 kinase was not modified. The p38 kinase inhibitor SB20358 significantly attenuated arachidonic acid‐ induced ERK and Akt activation, whereas the MEK inhibitor PD98059 had no inhibitory effect on Akt and p38 kinase activation in response to arachidonic acid in these cells. In addition, pertussis toxin (Gi inhibitor) and cholera toxin (Gs inhibitor) were without effect. Akt activation was also inhibited by the EGFR kinase inhibitor AG1478 and the Src kinase family inhibitor PP2, suggesting that the EGFR and c‐Src may too be critical in linking arachidonic acid’s effect on Akt signaling. Collectively, these findings demonstrate that arachidonic acid is a potent and direct activator of Akt in rabbit proximal tubular epithelium and demonstrate a critical upstream role of c‐Src, EGFR and p38 kinase in arachidonic acid‐ induced Akt activation independent of the classical heterotrimeric G protein coupled receptors pathways.