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.
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References
Nishizuka, Y. Nature 334, 661–665 (1988).
Aderem, A. A. et al. Nature 332, 362–364 (1988).
Wu, W. S., Walaas, S. I., Nairn, A. C. & Greengard, P. Proc. natn. Acad Sci. U.S.A. 79, 5249–5253 (1982).
Rozengurt, E., Rodriguez-Pena, M. & Smith, K. A. Proc. natn. Acad. Sci. U.S.A. 80, 7244–7248 (1983).
Blackshear, P. X., Wen, L., Glynn, B. P. & Witters, L. A. J. biol. Chem. 261, 1459–1469 (1986).
Graff, J. M., Gordon, J. I. & Blackshear, P. J. Science 246, 503–506 (1989).
Rosen, A., Keenan, K. F., Thelen, M., Nairn, A. C. & Aderem, A. A. J. exp. Med. 172, 1211–1215 (1990).
Graff, J. M., Young, T. M., Johnson, J. D. & Blackshear, P. J. J. biol. Chem. 264, 21818–21823 (1989).
Thelen, M., Rosen, A., Nairn, A. C. & Aderem, A. Proc. natn. Acad. Sci. U.S.A. 87, 5603–5607 (1990).
Dewald, B., Thelen, M. & Baggiolini, M. J. biol. Chem. 263, 16179–16184 (1988).
Bialojan, C. & Takai, A. Biochem. J. 256, 283–290 (1988).
Haystead, T. A. J. et al. Nature 337, 78–81 (1989).
Resh, M. D. Cell 58, 281–286 (1989).
Resh, M. D. & Ling, H. Nature 346, 84–86 (1990).
Veillette, A., Bookman, M. A., Horak, E. M. & Bolen, J. B. Cell 55, 301–308 (1988).
Borregaard, N., Heiple, J. M., Simons, E. R. & Clark, R. A. J. Cell Biol. 97, 52–61 (1983).
Rosen, A., Nairn, A. C., Greengard, P., Cohn, Z. A. & Aderem, A. A. J. biol. Chem. 264, 9118–9121 (1989).
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Thelen, M., Rosen, A., Nairn, A. et al. Regulation by phosphorylation of reversible association of a myristoylated protein kinase C substrate with the plasma membrane. Nature 351, 320–322 (1991). https://doi.org/10.1038/351320a0
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DOI: https://doi.org/10.1038/351320a0
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