Regulation by phosphorylation of reversible association of a myristoylated protein kinase C substrate with the plasma membrane.
Protein kinase C (PKC) transduces receptor-mediated signals by phosphorylating membrane-bound substrates which then act as effectors of specific cellular responses. The myristoylated alanine-rich C kinase substrate (MARCKS) is a specific PKC substrate which has been implicated in macrophage activation, neuro-secretion and growth factor-dependent mitogenesis. Myristoylation of MARCKS is required for effective binding to the plasma membrane where it colocalizes with PKC. 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.
Thelen
M
M
Rockefeller University, New York, New York.
Rosen
A
A
Nairn
A C
AC
Aderem
A
A
D000255:Adenosine Triphosphate / Q000378:metabolism; D001345:Autoradiography; D002462:Cell Membrane / Q000378:metabolism; D004789:Enzyme Activation; D004988:Ethers, Cyclic / Q000494:pharmacology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007700:Kinetics; D008565:Membrane Proteins; D019814:Myristic Acid; D009227:Myristic Acids / Q000378:metabolism; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D019319:Okadaic Acid; D010761:Phosphorus Radioisotopes; D010766:Phosphorylation; D011493:Protein Kinase C / Q000097:blood*; D011506:Proteins / Q000378:metabolism*; D014316:Tritium
D004988:Ethers, Cyclic; D047908:Intracellular Signaling Peptides and Proteins; C000619710:MARCKS protein, human; D008565:Membrane Proteins; D009227:Myristic Acids; D010761:Phosphorus Radioisotopes; D011506:Proteins; D019814:Myristic Acid; D014316:Tritium; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D019319:Okadaic Acid; D009240:N-Formylmethionine Leucyl-Phenylalanine; D000255:Adenosine Triphosphate; D011493:Protein Kinase C