Phosphoinositide-3 kinase binds to a proline-rich motif in the Na+, K+-ATPase alpha subunit and regulates its trafficking.
Enviado por Guillermo Yudowski el
Título | Phosphoinositide-3 kinase binds to a proline-rich motif in the Na+, K+-ATPase alpha subunit and regulates its trafficking. |
Publication Type | Journal Article |
Year of Publication | 2000 |
Autores | Yudowski, GA, Efendiev, R, Pedemonte, CH, Katz, AI, Berggren, PO, Bertorello, AM |
Journal | Proc Natl Acad Sci U S A |
Volume | 97 |
Issue | 12 |
Pagination | 6556-61 |
Date Published | 2000 Jun 6 |
ISSN | 0027-8424 |
Palabras clave | Amino Acid Motifs, Animals, Binding Sites, Cell Line, Dopamine, Endocytosis, Opossums, Peptides, Phosphatidylinositol 3-Kinases, Phosphorylation, Proline-Rich Protein Domains, Serine, Sodium-Potassium-Exchanging ATPase, src Homology Domains |
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. |
DOI | 10.1073/pnas.100128297 |
Alternate Journal | Proc. Natl. Acad. Sci. U.S.A. |
PubMed ID | 10823893 |
PubMed Central ID | PMC18657 |
Grant List | DK53460 / DK / NIDDK NIH HHS / United States |