HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 287/5/C1256    most recent 00229.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (5) Citing Articles via Google Scholar Google Scholar Articles by Chen, Y. Articles by Reuss, L. Search for Related Content PubMed PubMed Citation Articles by Chen, Y. Articles by Reuss, L.

MEMBRANE TRANSPORTERS, ION CHANNELS, AND PUMPS

Mechanism of activation of Xenopus CFTR by stimulation of PKC

Sealy Center for Structural Biology and Department of Neuroscience and Cell Biology, The University of Texas Medical Branch, Galveston, Texas 77555-0437

Submitted 10 May 2004 ; accepted in final form 25 June 2004

PKA-mediated phosphorylation of the regulatory (R) domain plays a major role in the activation of the human cystic fibrosis transmembrane conductance regulator (hCFTR). In contrast, the effect of PKC-mediated phosphorylation is controversial, smaller than that of PKA, and dependent on the cell type. In the present study, we expressed Xenopus CFTR (XCFTR) and hCFTR in Xenopus oocytes and examined their responses (i.e., macroscopic membrane conductance) to maximal stimulation by PKC and PKA agonists. With XCFTR, the average response to PKC was approximately sixfold that of PKA stimulation. In contrast, with hCFTR, the response to PKC was 90% of the response to PKA stimulation. The reason for these differences was the small response of XCFTR to PKA stimulation. Using the substituted cysteine accessibility method, we found no evidence for insertion of functional CFTR channels in the plasma membrane in response to PKC stimulation. The increase in macroscopic conductance in response to PKC stimulation of XCFTR was due to an approximately fivefold increase in single-channel open probability, with a minor (30%) increase in single-channel conductance. The responses of XCFTR to PKC stimulation and of hCFTR to PKA stimulation were mediated by similar increases in P_o. In both instances, there were no changes in the number of channels in the membrane. We speculate that in animals other than humans, PKC stimulation may be the dominant mechanism for activation of CFTR.

chloride channel; channel regulation; cystic fibrosis transmembrane conductance regulator gating; cystic fibrosis; phosphorylation; protein kinase A

This article has been cited by other articles:

				C. Perry, J. Blaine, H. Le, and I. I. Grichtchenko PMA- and ANG II-induced PKC regulation of the renal Na+-HCO3- cotransporter (hkNBCe1) Am J Physiol Renal Physiol, February 1, 2006; 290(2): F417 - F427. [Abstract] [Full Text] [PDF]

				S. G. Bompadre, T. Ai, J. H. Cho, X. Wang, Y. Sohma, M. Li, and T.-C. Hwang CFTR Gating I: Characterization of the ATP-dependent Gating of a Phosphorylation-independent CFTR Channel ({Delta}R-CFTR) J. Gen. Physiol., March 28, 2005; 125(4): 361 - 375. [Abstract] [Full Text] [PDF]

				Y. Chen, B. Button, G. A. Altenberg, and L. Reuss Potentiation of effect of PKA stimulation of Xenopus CFTR by activation of PKC: role of NBD2 Am J Physiol Cell Physiol, November 1, 2004; 287(5): C1436 - C1444. [Abstract] [Full Text] [PDF]