Abstract
A rise in the concentration of cyclic AMP inhibits secretion in human platelets1–3. In mammalian cells the mechanism of action of cyclic AMP involves activation of a protein kinase and results in protein phosphorylation4. It has previously been shown that myosin light chain kinase purified from smooth muscle is a substrate for the catalytic subunit of cyclic AMP-dependent protein kinase5 and that phosphorylation of smooth muscle myosin kinase results in a decrease in its activity6. Here we present evidence that platelet myosin kinase is a substrate for the catalytic subunit of protein kinase and that phosphorylation of this myosin kinase, isolated from a non-muscle cell, decreases the activity of this enzyme. Dephosphorylation of platelet myosin kinase by a purified phosphatase7 restores its original activity. A decrease in myosin kinase activity in platelets would increase the relative amount of unphosphorylated myosin, which unlike phosphorylated myosin, cannot interact with actin8,9. These findings suggest a mechanism by which cyclic AMP might modulate actin–myosin interaction in platelets and other non-muscle cells.
Access options
Subscribe to Journal
Get full journal access for 1 year
220,50 €
only 4,32 € per issue
All prices include VAT for France.
Rent or Buy article
Get time limited or full article access on ReadCube.
from$8.99
All prices are NET prices.
References
- 1.
Haslam, R. J. & Lynham, J. A. Biochem. biophys. Res. Commun. 77, 714–722 (1977).
- 2.
Haslam, R. J. & Lynham, J. A. Thromb. Res. 12, 619–628 (1978).
- 3.
Haslam, R. J., Lynham, J. A. & Fox, J. E. B. Biochem. J. 178, 397–407 (1979).
- 4.
Krebs, E. G. & Beavo, J. A. A. Rev. Biochem. 48, 923–959 (1979).
- 5.
Adelstein, R. S., Conti, M. A., Hathaway, D. R. & Klee, C. B. J. biol. Chem. 253, 8347–8350 (1978).
- 6.
Conti, M. A. & Adelstein, R. S. J. biol. Chem. 256, 3178–3182 (1981).
- 7.
Pato, M. D. & Adelstein, R. S. J. biol. Chem. 255, 6535–6538 (1980).
- 8.
Adelstein, R. S. & Conti, M. A. Nature 256, 597–598 (1975).
- 9.
Lebowitz, E. A. & Cooke, R. J. biol. Chem. 253, 5443–5447 (1978).
- 10.
Hathaway, D. R. & Adelstein, R. S. Proc. natn. Acad. Sci. U.S.A. 76, 1653–1657 (1979).
- 11.
Dabrowska, R. & Hartshorne, D. J. Biochem. biophys. Res. Commun. 85, 1352–1359 (1978).
- 12.
Scordilis, S. P. & Adelstein, R. S. J. biol. Chem. 253, 9041–9048 (1978).
- 13.
Trotter, J. A. & Adelstein, R. S. J. biol. Chem. 254, 8781–8785 (1979).
- 14.
Yerna, M.-J., Aksoy, M. O., Hartshorne, D. J. & Goldman, R. D. J. Cell Sci. 31, 411–429 (1978).
- 15.
Scholey, J. M., Taylor, K. A. & Kendrick-Jones, J. Nature 287, 233–235 (1980).
- 16.
Kerrick, W. G. L., Hoar, P. E., Cassidy, P. S. & Malencik, D. A. Regulation of Muscle Contraction: Excitation–Contraction Coupling (eds Grinnell, A. D. & Brazier, M. A. B.) 227–239 (Academic, New York, 1980).
- 17.
Daniel, J. L., Molish, I. R., Holmsen, H. & Salganicoff, L. Cold Spring Harb. Conf. Cell Proliferation Vol. 8 (in the press).
- 18.
Walsh, D. A. et al. J. biol. Chem. 246, 1977–1985 (1971).
- 19.
Klee, C. B. Biochemistry 16, 1017–1024 (1977).
Author information
Author notes
- D. R. Hathaway
Present address: Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana 46223, USA.
Affiliations
Section on Molecular Cardiology, Cardiology Branch, National Heart, Lung, and Blood Institute, Building 10, Room 7B–15, National Institutes of Health, Bethesda, Maryland 20205, USA
- D. R. Hathaway
- , C. R. Eaton
- & R. S. Adelstein
Authors
Search for D. R. Hathaway in:
Search for C. R. Eaton in:
Search for R. S. Adelstein in:
Rights and permissions
To obtain permission to re-use content from this article visit RightsLink.
About this article
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.
