![]()
|
|
||||||||
J. Biol. Chem., Vol. 276, Issue 20, 17339-17346, May 18, 2001
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the Medical and Research Services of the Ralph H. Johnson
Veterans Affairs Medical Center, and Departments of Medicine
( We used a cultured murine cell model of the
inner medullary collecting duct (mIMCD-3 cells) to examine the
regulation of the ubiquitous sodium-proton exchanger,
Na+/H+ exchanger isoform 1 (NHE-1), by a
prototypical G protein-coupled receptor, the bradykinin B2
receptor. Bradykinin rapidly activates NHE-1 in a
concentration-dependent manner as assessed by proton microphysiometry of quiescent cells and by
2'-7'-bis[2-carboxymethyl]-5(6)-carboxyfluorescein fluorescence measuring the accelerated rate of pHi recovery from an imposed acid load. The activation of NHE-1 is blocked by
inhibitors of the bradykinin B2 receptor, phospholipase C, Ca2+/calmodulin (CaM), and Janus kinase 2 (Jak2),
but not by pertussis toxin or by inhibitors of protein kinase C and
phosphatidylinositol 3'-kinase. Immunoprecipitation studies showed that
bradykinin stimulates the assembly of a signal transduction complex
that includes CaM, Jak2, and NHE-1. CaM appears to be a direct
substrate for phosphorylation by Jak2 as measured by an in
vitro kinase assay. We propose that Jak2 is a new indirect
regulator of NHE-1 activity, which modulates the activity of NHE-1 by
increasing the tyrosine phosphorylation of CaM and most likely by
increasing the binding of CaM to NHE-1.
Bradykinin B2 Receptors Activate
Na+/H+ Exchange in mIMCD-3 Cells via Janus
Kinase 2 and Ca2+/Calmodulin*
,
,
,
,
,
,
,
, and
Nephrology and § Endocrinology Divisions) and
¶ Pharmacology of the Medical University of South Carolina,
Charleston, South Carolina 29425
*
This work was supported by grants from the Department of
Veterans Affairs (Merit Awards to M. N. G., D. W. P., and
J. R. R. and a REAP Award to Y. V. M., A. A. J., J. R. R., and
M. N. G.), National Institutes of Health Grants DK52448 (to
J. R. R.) and K01-DK02694 (to Y. V. M.), laboratory endowments
jointly supported by the Medical University of South Carolina Division
of Nephrology and Dialysis Clinics, Incorporated (to D. W. P. and
J. R. R.), an American Heart Association Fellowship Award (to
Y. V. M.), and a Medical University of South Carolina University
Research Foundation award (to M. N. G.). The FLIPRTM is a shared
Medical University of South Carolina resource obtained with Public
Health Service Grant S10 RR13005. The microphysiometer is a shared
Veterans Affairs resource obtained with a Veterans Affairs large
equipment grant.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: Rm. 829 CSB,
Medical University of South Carolina, 171 Ashley Ave., Charleston, SC
29425-2227. Tel.: 843-876-5128; Fax: 843-792-8399; E-mail: garnovsk@musc.edu.
This article has been cited by other articles:
![]() |
J. Xue, D. Zhou, H. Yao, O. Gavrialov, M. J. McConnell, B. D. Gelb, and G. G. Haddad Novel functional interaction between Na+/H+ exchanger 1 and tyrosine phosphatase SHP-2 Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2007; 292(6): R2406 - R2416. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. H. Turner, M. N. Garnovskaya, S. D. Coaxum, T. M. Vlasova, M. Yakutovich, D. M. Lefler, and J. R. Raymond Ca2+-Calmodulin and Janus Kinase 2 Are Required for Activation of Sodium-Proton Exchange by the Gi-Coupled 5-Hydroxytryptamine1a Receptor J. Pharmacol. Exp. Ther., January 1, 2007; 320(1): 314 - 322. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y. V. Mukhin, M. Gooz, J. R. Raymond, and M. N. Garnovskaya Collagenase-2 and -3 Mediate Epidermal Growth Factor Receptor Transactivation by Bradykinin B2 Receptor in Kidney Cells J. Pharmacol. Exp. Ther., September 1, 2006; 318(3): 1033 - 1043. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. M. Tiwari, P. L. Prather, and P. R. Mayeux Mechanism of Bradykinin-Induced Ca2+ Mobilization in Murine Proximal Tubule Epithelial Cells J. Pharmacol. Exp. Ther., May 1, 2005; 313(2): 798 - 805. [Abstract] [Full Text] [PDF] |
||||
![]() |
S.-L. Xia, L. Wang, M. N. Cash, X. Teng, R. A. Schwalbe, and C. S. Wingo Extracellular ATP-induced calcium signaling in mIMCD-3 cells requires both P2X and P2Y purinoceptors Am J Physiol Renal Physiol, August 1, 2004; 287(2): F204 - F214. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. N. Garnovskaya, Y. V. Mukhin, T. M. Vlasova, and J. R. Raymond Hypertonicity Activates Na+/H+ Exchange through Janus Kinase 2 and Calmodulin J. Biol. Chem., May 2, 2003; 278(19): 16908 - 16915. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y. V. Mukhin, E. A. Garnovsky, M. E. Ullian, and M. N. Garnovskaya Bradykinin B2 Receptor Activates Extracellular Signal-Regulated Protein Kinase in mIMCD-3 Cells via Epidermal Growth Factor Receptor Transactivation J. Pharmacol. Exp. Ther., March 1, 2003; 304(3): 968 - 977. [Abstract] [Full Text] [PDF] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |