Fibroblast growth factor-10 upregulates Na,K-ATPase via the MAPK pathway.
We studied the effects of fibroblast growth factor (FGF-10) on alveolar epithelial cell (AEC) Na,K-ATPase regulation. Within 30 min FGF-10 increased Na,K-ATPase activity and alpha1 protein abundance by 2.5-fold at the AEC plasma membrane. Pretreatment of AEC with the mitogen-activated protein kinase (MAPK) inhibitor U0126, a Grb2-SOS inhibitor (SH3-b-p peptide), or a Ras inhibitor (farnesyl transferase inhibitor (FTI 277)), as well as N17-AEC that express a Ras dominant negative protein each prevented FGF-10-mediated Na,K-ATPase recruitment to the AEC plasma membrane. Accordingly, we provide first evidence that FGF-10 upregulates (short-term) the Na,K-ATPase activity in AEC via the Grb2-SOS/Ras/MAPK pathway.
Upadhyay
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Division of Pulmonary and Critical Care Medicine, Northwestern University Medical School, Chicago, IL 60611, USA. upadhyayd@pol.net
Lecuona
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E
Comellas
A
A
Kamp
D W
DW
Sznajder
J I
JI
D002070:Butadienes / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000201:enzymology / Q000502:physiology; D051526:Fibroblast Growth Factor 10; D005346:Fibroblast Growth Factors / Q000502:physiology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008715:Methionine / Q000031:analogs & derivatives* / Q000494:pharmacology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008954:Models, Biological; D009570:Nitriles / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D018631:ras Proteins / Q000502:physiology
D002070:Butadienes; D004791:Enzyme Inhibitors; C496463:FGF10 protein, human; C096856:FTI 277; D051526:Fibroblast Growth Factor 10; D009570:Nitriles; C113580:U 0126; D005346:Fibroblast Growth Factors; D008715:Methionine; D020928:Mitogen-Activated Protein Kinases; D018631:ras Proteins; D000254:Sodium-Potassium-Exchanging ATPase