Abstract
The (Na,K)ATPase is responsible for generating the ionic gradients and membrane potentials by the exchange of intracellular Na+ for K+. It has been recently shown that (Na,K)ATPase is involved in the exocytic pathway of basic fibroblast growth factor (bFGF), although it is not known that bFGF is secreted to the outside of cell through direct interaction with (Na,K) ATPase. To understand the role for (Na,K)ATPase in the secretory pathway of bFGF, we have sought to identify the cytoplasmic domains of the α1 isoform of (Na,K)ATPase interacting with bFGF by yeast two-hybrid system. We have also investigated the interaction between the α2 isoform of (Na,K)ATPase and bFGF to find out whether the interaction is isorm-specific. We found that none of the cytoplasmic domains of (Na,K)ATPase isoforms interacted with bFGF. The result suggests that the interaction between bFGF and (Na,K)ATPase might be indirect, thus requiring other proteins which are involved in the formation of protein complexes for the interaction, although we cannot exclude the possibility that the interaction requires the element of the whole α subunit structure that was not present in the isolated α subunit cytoplasmic domains.
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References Cited
Burgess, W. H. and Maciag, T., The heparin-binding (fibroblast) growth factor family of proteins.Annu. Rev. Biochem., 58, 575–606 (1989).
Florkiewicz, R. Z., Majack, R. A., Buechler, R. D. and Florkiewicz, E., Quantitative export of FGF-2 occurs through an alternative, energy-dependent, non-ER/Golgi pathway.J. Cell. Physiol., 162, 388–399 (1995).
Florkiewicz, R. Z., Anchin, J. and Baird, A., The inhibition of fibroblast growth factor-2 export by cardenolides implies a novel function for the catalytic subunit of Na+, K+-ATPase.J. Biol. Chem., 273, 544–551 (1998).
Friesel, R. E. and Maciag, T., Molecular mechanisms of angiogenesis: fibroblast growth factor signal transduction.FASEB J., 9, 919–925 (1995).
Gietz, D., St. Jean, A., Wood, R. A. and Schiestl, R. H., Improved methods for high efficiency transformation of intact yeast cells.Nucleic Acids Res., 20, 1425 (1992).
Jorgensen, D. L., Mechanism of the Na+, K+ pump: protein structure and conformation of the pure (Na+, K+)-ATPase.Biochim. Biophys. Acta, 694, 27–68 (1982).
Jorgensen, D. L. and Anderson, J. P., Thermoinactivation and aggregation of alpha beta units in soluble and membrane-bound (Na,K)ATPase.Biochemistry, 25, 2889–2897 (1986).
Karsan, A., Yee, E., Poirier, G. G., Zhou, P., Crag, R. and Harlan, J. M., Fibroblast growth factor-2 inhibits endothelial cell apoptosis by Bcl-2-dependent and independent mechanism.Am. J. Pathol., 151, 1775–1784 (1997).
Laemli, U. K., Cleavage of structural proteins during the assembly of the head of bacteriophage T4.Nature, 227, 680–685 (1970).
Lingrel, J. B. and Kuntzweiler, T., Na+,K+-ATPase.J. Biol. Chem., 269, 19659–19662 (1994).
McNeil, P. L., Muthukrishnan, L., Warder, E. and D’Amore, D., Growth factors are released by mechanically wounded endothelial cells.J. Cell Biol., 109, 811–822 (1989).
Mignatti, P., Morimoto, T. and Rifkin, D. B., Basic fibroblast growth factor, a protein devoid of secretory signal sequence, is released by cells via a pathway independent of the endoplasmic reticulum-Golgi complex.J. Cell. Physiol., 151, 81–93 (1992).
Muesch, A., Hartmann, E., Rubartelli, A., Sita, R. and Rapoport, T. M., A novel pathway for secretory proteins.Trends Biochem. Sci., 15, 86–88 (1990).
Muthukrishnan, L., Warder, E. and McNeil, P., Basic fibroblast growth factor is efficiently released from a cytosolic storage site through plasma membrane disruptions of endothelial cells.J. Cell. Physiol., 148, 1–16 (1991).
Schwartz, A., Lindenmayer, G. E. and Allen, J. C., The sodium-potassium adenosine triphosphatase: physiological and biochemical aspects.Pharmacol. Rev., 27, 3–134 (1975).
Shamraj, O. I. and Lingrel, J. B., A putative fourth Na+, K+-ATPase alpha-subunits gene is expressed in testis.Proc. Natl. Acad. Sci. U.S.A., 91, 12952–12956 (1994).
Shull, G. E., Schwartz, A. and Lingrel, J. B., Aminoacid sequence of the catalytic subunit of the (Na+, K+) ATPase.Nature, 316, 691–695 (1985).
Vasilets, L. A. and Schwartz, W., Structure-function relationships of cation binding in the Na+,K+-ATPase.Biochim. Biophys. Acta, 1154, 201–222 (1993).
Yoon, K. L. and Guidotti, G..Studies on the membrane topology of the (Na,K)ATPase.J. Biol. Chem., 268, 28249–28258 (1994).
Yoon, T. S. and Lee, K. L., Isoform-specific interaction of the cytoplasmic domains of Na,K-ATPase.Molecules and Cells (in press).
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Oh, J., Lee, K. Possible implication for an indirect interaction between basic fibroblast growth factor and (Na,K)ATPase. Arch. Pharm. Res. 21, 707–711 (1998). https://doi.org/10.1007/BF02976762
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DOI: https://doi.org/10.1007/BF02976762