Phosphoinositide-3 kinase binds to a proline-rich motif in the Na+K+-ATPase α subunit and regulates its trafficking

摘要

Endocytosis of Na⁺,K⁺-ATPase molecules in response to G protein-coupled receptor stimulation requires activation of class IA phosphoinositide-3 kinase (PI3K-IA) in a protein kinase C-dependent manner. In this paper, we report that PI3K-IA, through its p85α subunit-SH3 domain, binds to a proline-rich region in the Na⁺,K⁺-ATPase catalytic α subunit. This interaction is enhanced by protein kinase C-dependent phosphorylation of a serine residue that flanks the proline-rich motif in the Na⁺,K⁺-ATPase α subunit and results in increased PI3K-IA activity, an effect necessary for adaptor protein 2 binding and clathrin recruitment. Thus, Ser-phosphorylation of the Na⁺,K⁺-ATPase catalytic subunit serves as an anchor signal for regulating the location of PI3K-IA and its activation during Na⁺,K⁺-ATPase endocytosis in response to G protein-coupled receptor signals.