|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 276, Issue 34, 31535-31541, August 24, 2001
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the Department of Biochemistry and Medicine, McGill
University, Montreal, Quebec H3G 1A4, Canada
Previous studies showed that the
Mechanistic Basis for Kinetic Differences between the
Rat
1, 2, and 3 Isoforms of the Na,K-ATPase*
1, 2, and
3 isoforms of the catalytic subunit of the Na,K-ATPase differ in
their apparent affinities for the ligands ATP, Na+,
and K+. For the rat isoforms transfected into HeLa cells,
K'ATP for ATP binding at its low affinity site
is lower for 2 and 3 compared with 1; relative to 1 and
2, 3 has a higher K'Na and lower K'K (Jewell, E. A., and Lingrel,
J. B (1991) J. Biol. Chem. 266, 16925-16930;
Munzer, J. S., Daly, S. E., Jewell-Motz, E. A., Lingrel, J. B, and Blostein, R. (1994) J. Biol.
Chem. 269, 16668-16676). The experiments described in the
present study provide insight into the mechanistic basis for these
differences. The results show that 2 differs from 1 primarily by
a shift in the E1 
E2 equilibrium in favor of
E1 form(s) as evidenced by (i) a ~20-fold increase in IC50 for vanadate, (ii) decreased catalytic
turnover, and (iii) notable stability of Na,K-ATPase activity at acidic pH. In contrast, despite its lower K'ATP
compared with 1, the E1 E2 poise of 3 is not shifted toward
E1. Distinct intrinsic interactions with
Na+ ions are underscored by the marked selectivity for
Na+ over Li+ of 3 compared with either 1
or 2 and higher K'Na for cytoplasmic Na+, which persists over a 100-fold range in proton
concentration, independent of the presence of K+. The
kinetic analysis also suggests 3-specific differences in relative
rates of partial reactions, which impact this isoform's distinct
apparent affinities for both Na+ and K+.
*
This work was supported by grants from the Medical Research
Council of Canada and Quebec Heart and Stroke Foundation (to R. B.).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.
Supported by a predoctoral traineeship from the Heart and Stroke
Foundation of Canada.
Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  A. Edwards and T. L. Pallone Ouabain modulation of cellular calcium stores and signaling Am J Physiol Renal Physiol, November 1, 2007; 293(5): F1518 - F1532. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Edwards and T. L. Pallone Modification of cytosolic calcium signaling by subplasmalemmal microdomains Am J Physiol Renal Physiol, June 1, 2007; 292(6): F1827 - F1845. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. E. Moseley, M. T. Williams, T. L. Schaefer, C. S. Bohanan, J. C. Neumann, M. M. Behbehani, C. V. Vorhees, and J. B Lingrel Deficiency in Na,K-ATPase {alpha} Isoform Genes Alters Spatial Learning, Motor Activity, and Anxiety in Mice J. Neurosci., January 17, 2007; 27(3): 616 - 626. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K Wagoner, G Sanchez, A-N Nguyen, G C Enders, and G Blanco Different expression and activity of the {alpha}1 and {alpha}4 isoforms of the Na,K-ATPase during rat male germ cell ontogeny Reproduction, November 1, 2005; 130(5): 627 - 641. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Segall, A. Mezzetti, R. Scanzano, J. J. Gargus, E. Purisima, and R. Blostein Alterations in the {alpha}2 isoform of Na,K-ATPase associated with familial hemiplegic migraine type 2 PNAS, August 2, 2005; 102(31): 11106 - 11111. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Segall, R. Scanzano, M. A. Kaunisto, M. Wessman, A. Palotie, J. J. Gargus, and R. Blostein Kinetic Alterations due to a Missense Mutation in the Na,K-ATPase {alpha}2 Subunit Cause Familial Hemiplegic Migraine Type 2 J. Biol. Chem., October 15, 2004; 279(42): 43692 - 43696. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Segall, Z. Z. Javaid, S. L. Carl, L. K. Lane, and R. Blostein Structural Basis for alpha 1 Versusalpha 2 Isoform-distinct Behavior of the Na,K-ATPase J. Biol. Chem., March 7, 2003; 278(11): 9027 - 9034. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. E. Moseley, S. P. Lieske, R. K. Wetzel, P. F. James, S. He, D. A. Shelly, R. J. Paul, G. P. Boivin, D. P. Witte, J. M. Ramirez, et al. The Na,K-ATPase alpha 2 Isoform Is Expressed in Neurons, and Its Absence Disrupts Neuronal Activity in Newborn Mice J. Biol. Chem., February 7, 2003; 278(7): 5317 - 5324. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. A. Golovina, H. Song, P. F. James, J. B. Lingrel, and M. P. Blaustein Na+ pump alpha 2-subunit expression modulates Ca2+ signaling Am J Physiol Cell Physiol, February 1, 2003; 284(2): C475 - C486. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. F. Hoffman, A. Wickrema, O. Potapova, M. Milanick, and D. R. Yingst Na pump isoforms in human erythroid progenitor cells and mature erythrocytes PNAS, October 29, 2002; 99(22): 14572 - 14577. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-D. Horisberger and S. Kharoubi-Hess Functional differences between {alpha} subunit isoforms of the rat Na,K-ATPase expressed in Xenopus oocytes J. Physiol., March 15, 2002; 539(3): 669 - 680. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-D. Horisberger and S. Kharoubi-Hess Functional differences between {alpha} subunit isoforms of the rat Na,K-ATPase expressed in Xenopus oocytes J. Physiol., February 1, 2002; (2002) 200101320. [Abstract] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |