title: Phosphoinositide-3 kinase binds to a proline-rich motif in the Na+, K+-ATPase alpha subunit and regulates its trafficking.
abstract: Endocytosis of Na(+),K(+)-ATPase molecules in response to G protein-coupled receptor stimulation requires activation of class I(A) phosphoinositide-3 kinase (PI3K-I(A)) in a protein kinase C-dependent manner. In this paper, we report that PI3K-I(A), through its p85alpha subunit-SH3 domain, binds to a proline-rich region in the Na(+),K(+)-ATPase catalytic alpha 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 alpha subunit and results in increased PI3K-I(A) 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-I(A) and its activation during Na(+),K(+)-ATPase endocytosis in response to G protein-coupled receptor signals.
authors.affiliation: The Rolf Luft Center for Diabetes Research, Karolinska Hospital, Department of Molecular Medicine, Karolinska Institutet, S-17176 Stockholm, Sweden.
authors.forename: G A
authors.initials: GA
authors.lastname: Yudowski
authors.forename: R
authors.initials: R
authors.lastname: Efendiev
authors.forename: C H
authors.initials: CH
authors.lastname: Pedemonte
authors.forename: A I
authors.initials: AI
authors.lastname: Katz
authors.forename: P O
authors.initials: PO
authors.lastname: Berggren
authors.forename: A M
authors.initials: AM
authors.lastname: Bertorello
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D004298:Dopamine / Q000494:pharmacology; D004705:Endocytosis; D009893:Opossums; D010455:Peptides / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D010766:Phosphorylation; D055232:Proline-Rich Protein Domains; D012694:Serine / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D018909:src Homology Domains
chemical_list: D004298:Dopamine; D010455:Peptides; D019869:Phosphatidylinositol 3-Kinases; D012694:Serine; D000254:Sodium-Potassium-Exchanging ATPase