Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-1400
Bagorda, A; Guerra, L; Di Sole, F; Hemle-Kolb, C; Cardone, R A; Fanelli, T; Reshkin, S J; Gisler, S M; Murer, H; Casavola, V (2002). Reciprocal protein kinase A regulatory interactions between cystic fibrosis transmembrane conductance regulator and Na+/H+ exchanger isoform 3 in a renal polarized epithelial cell model. Journal of Biological Chemistry, 277(24):21480-21488.
Although Cystic fibrosis transmembrane conductance regulator (CFTR) has been shown to regulate the activity of NHE3, the potential reciprocal interaction of NHE3 to modulate the protein kinase A (PKA)-dependent regulation of CFTR in epithelial cells is still unknown. In the present work, we describe experiments to define the interactions between CFTR and NHE3 with the regulatory, scaffolding protein, NHERF that organize their PKA-dependent regulation in a renal epithelial cell line that expresses endogenous CFTR. The expression of rat NHE3 significantly decreased PKA-dependent activation of CFTR without altering CFTR expression, and this decrease was prevented by mutation of either of the two rat NHE3 PKA target serines to alanine (S552A or S605A). Inhibition of CFTR expression by antisense treatment resulted in an acute decrease in PKA-dependent regulation of NHE3 activity. CFTR, NHE3, and ezrin were recognized by NHERF-2 but not NHERF-1 in glutathione S-transferase pull-down experiments. Ezrin may function as a protein kinase A anchoring protein (AKAP) in this signaling complex, because blocking the binding of PKA to an AKAP by incubation with the S-Ht31 peptide inhibited the PKA-dependent regulation of CFTR in the absence of NHE3. In the A6-NHE3 cells S-Ht31 blocked the PKA regulation of NHE3 whereas it now failed to affect the regulation of CFTR. We conclude that CFTR and NHE3 reciprocally interact via a shared regulatory complex comprised of NHERF-2, ezrin, and PKA.
|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||04 Faculty of Medicine > Institute of Physiology|
07 Faculty of Science > Institute of Physiology
|DDC:||570 Life sciences; biology|
|Date:||14 June 2002|
|Deposited On:||11 Feb 2008 12:23|
|Last Modified:||27 Nov 2013 19:04|
|Publisher:||American Society for Biochemistry and Molecular Biology|
|Additional Information:||This research was originally published in Bagorda, A; Guerra, L; Di Sole, F; Hemle-Kolb, C; Cardone, R A; Fanelli, T; Reshkin, S J; Gisler, S M; Murer, H; Casavola, V. Reciprocal protein kinase A regulatory interactions between cystic fibrosis transmembrane conductance regulator and Na+/H+ exchanger isoform 3 in a renal polarized epithelial cell model. J. Biol. Chem. 2002, 277(24):21480-8. © the American Society for Biochemistry and Molecular Biology.|
|Citations:||Web of Science®. Times Cited: 30|
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