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

Guillermo A. Yudowski, Riad Efendiev, Carlos H. Pedemonte, Adrian I. Katz, Per Olof Berggren, Alejandro M. Bertorello

Research output: Contribution to journalArticle

144 Scopus citations

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 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-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.

Original languageEnglish
Pages (from-to)6556-6561
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume97
Issue number12
DOIs
StatePublished - Jun 6 2000
Externally publishedYes

    Fingerprint

ASJC Scopus subject areas

  • Genetics
  • General

Cite this