Regulation by phosphorylation of reversible association of a myristoylated protein kinase C substrate with the plasma membrane

Marcus Thelen, Antony Rosen, Angus C. Nairn, Alan Aderem

Research output: Contribution to journalArticle

Abstract

PROTEIN kinase C (PKC) transduces receptor-mediated signals by phosphorylating membrane-bound substrates which then act as effectors of specific cellular responses1. The myristoylated alaninerich C kinase substrate (MARCKS) is a specific PKC substrate which has been implicated in macrophage activation, neuro-secretion and growth factor-dependent mitogenesis2-5. Myristoylation of MARCKS is required for effective binding to the plasma membrane6 where it colocalizes with PKC7. Here we report that PKC-dependent phosphorylation displaces MARCKS from the membrane and that its subsequent dephosphorylation is accompanied by its reassociation with the membrane. This cycle of phosphorylation-dependent membrane attachment and detachment of a myristoylated protein represents a novel mechanism of reversible membrane targeting. As MARCKS is a calmodulin- and actin-binding protein (ref. 8, and J. Hartwig et al., manuscript submitted), the cycle of membrane attachment/detachment represents a mechanism through which PKC might reversibly regulate actin-membrane interaction.

Original languageEnglish (US)
Pages (from-to)320-322
Number of pages3
JournalNature
Volume351
Issue number6324
StatePublished - May 23 1991
Externally publishedYes

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Protein Kinase C
Phosphotransferases
Phosphorylation
Cell Membrane
Membranes
Calmodulin-Binding Proteins
Microfilament Proteins
Macrophage Activation
Manuscripts
Actins
Intercellular Signaling Peptides and Proteins
Proteins

ASJC Scopus subject areas

  • General

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Regulation by phosphorylation of reversible association of a myristoylated protein kinase C substrate with the plasma membrane. / Thelen, Marcus; Rosen, Antony; Nairn, Angus C.; Aderem, Alan.

In: Nature, Vol. 351, No. 6324, 23.05.1991, p. 320-322.

Research output: Contribution to journalArticle

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N2 - PROTEIN kinase C (PKC) transduces receptor-mediated signals by phosphorylating membrane-bound substrates which then act as effectors of specific cellular responses1. The myristoylated alaninerich C kinase substrate (MARCKS) is a specific PKC substrate which has been implicated in macrophage activation, neuro-secretion and growth factor-dependent mitogenesis2-5. Myristoylation of MARCKS is required for effective binding to the plasma membrane6 where it colocalizes with PKC7. Here we report that PKC-dependent phosphorylation displaces MARCKS from the membrane and that its subsequent dephosphorylation is accompanied by its reassociation with the membrane. This cycle of phosphorylation-dependent membrane attachment and detachment of a myristoylated protein represents a novel mechanism of reversible membrane targeting. As MARCKS is a calmodulin- and actin-binding protein (ref. 8, and J. Hartwig et al., manuscript submitted), the cycle of membrane attachment/detachment represents a mechanism through which PKC might reversibly regulate actin-membrane interaction.

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