Possible implication for an indirect interaction between basic fibroblast growth factor and (Na,K)ATPase

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 isoform-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.