Regulation by phosphorylation of reversible association of a myristoylated protein kinase C substrate with the plasma membrane
- 1 May 1991
- journal article
- letter
- Published by Springer Nature in Nature
- Vol. 351 (6324) , 320-322
- https://doi.org/10.1038/351320a0
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 alanine-rich C kinase substrate (MARCKS) is a specific PKC substrate which has been implicated in macrophage activation, neurosecretion 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.Keywords
This publication has 17 references indexed in Scilit:
- Activation of protein kinase C results in the displacement of its myristoylated, alanine-rich substrate from punctate structures in macrophage filopodia.The Journal of Experimental Medicine, 1990
- Tumor necrosis factor alpha modifies agonist-dependent responses in human neutrophils by inducing the synthesis and myristoylation of a specific protein kinase C substrate.Proceedings of the National Academy of Sciences, 1990
- Myristoylated and Nonmyristoylated Forms of a Protein Are Phosphorylated by Protein Kinase CScience, 1989
- Specific and saturable binding of pp60v-src to plasma membranes: Evidence for a myristyl-src receptorCell, 1989
- Effects of the tumour promoter okadaic acid on intracellular protein phosphorylation and metabolismNature, 1989
- Inhibitory effect of a marine-sponge toxin, okadaic acid, on protein phosphatases. Specificity and kineticsBiochemical Journal, 1988
- The molecular heterogeneity of protein kinase C and its implications for cellular regulationNature, 1988
- Stimulus-dependent myristoylation of a major substrate for protein kinase CNature, 1988
- Phorbol esters, phospholipase C, and growth factors rapidly stimulate the phosphorylation of a Mr 80,000 protein in intact quiescent 3T3 cells.Proceedings of the National Academy of Sciences, 1983
- Calcium/phospholipid regulates phosphorylation of a Mr "87k" substrate protein in brain synaptosomes.Proceedings of the National Academy of Sciences, 1982