The Na,K-ATPase acts upstream of phosphoinositide PI(4,5)P₂ facilitating unconventional secretion of Fibroblast Growth Factor 2.

ABSTRACT: FGF2 is a tumor cell survival factor that is exported from cells by an ER/Golgi-independent secretory pathway. This unconventional mechanism of protein secretion is based on direct translocation of FGF2 across the plasma membrane. The Na,K-ATPase has previously been shown to play a role in this process, however, the underlying mechanism has remained elusive. Here, we define structural elements that are critical for a direct physical interaction between FGF2 and the α1 subunit of the Na,K-ATPase. In intact cells, corresponding FGF2 mutant forms were impaired regarding both recruitment at the inner plasma membrane leaflet and secretion. Ouabain, a drug that inhibits both the Na,K-ATPase and FGF2 secretion, was found to impair the interaction of FGF2 with the Na,K-ATPase in cells. Our finding

SUBMITTER: Legrand C 

PROVIDER: S-EPMC7096399 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature