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 Citations (Scopus)

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

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1-Phosphatidylinositol 4-Kinase
Proline
Phosphatidylinositol 3-Kinases
G-Protein-Coupled Receptors
Endocytosis
Protein Kinase C
Catalytic Domain
Phosphorylation
Clathrin
src Homology Domains
Protein Binding
Serine
sodium-translocating ATPase

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Phosphoinositide-3 kinase binds to a proline-rich motif in the Na+,K+- ATPase α subunit and regulates its trafficking. / Yudowski, Guillermo A.; Efendiev, Riad; Pedemonte, Carlos H.; Katz, Adrian I.; Berggren, Per Olof; Bertorello, Alejandro M.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 97, No. 12, 06.06.2000, p. 6556-6561.

Research output: Contribution to journalArticle

Yudowski, Guillermo A. ; Efendiev, Riad ; Pedemonte, Carlos H. ; Katz, Adrian I. ; Berggren, Per Olof ; Bertorello, Alejandro M. / Phosphoinositide-3 kinase binds to a proline-rich motif in the Na+,K+- ATPase α subunit and regulates its trafficking. In: Proceedings of the National Academy of Sciences of the United States of America. 2000 ; Vol. 97, No. 12. pp. 6556-6561.
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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.",
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AU - Yudowski, Guillermo A.

AU - Efendiev, Riad

AU - Pedemonte, Carlos H.

AU - Katz, Adrian I.

AU - Berggren, Per Olof

AU - Bertorello, Alejandro M.

PY - 2000/6/6

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N2 - 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.

AB - 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.

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