Phosphoinositide-3 kinase binds to a proline-rich motif in the Na+, K+-ATPase alpha subunit and regulates its trafficking |
| |
| Authors: | Yudowski G A Efendiev R Pedemonte C H Katz A I Berggren P O Bertorello A M |
| |
| Affiliation: | The Rolf Luft Center for Diabetes Research, Karolinska Hospital, Department of Molecular Medicine, Karolinska Institutet, S-17176 Stockholm, Sweden. |
| |
| 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. |
| |
| Keywords: | |
| 本文献已被 PubMed 等数据库收录！ |
|
