Advertisement

Is There a Function for Protein Carboxylmethylation in the Nervous System?

  • Melvin L. Billingsley
  • Randall L. Kincaid
  • Marina E. Wolf
  • Robert H. Roth
  • Walter Lovenberg
  • Carey D. Balaban
  • S. Milton
Chapter
Part of the Experimental Biology and Medicine book series (EBAM, volume 12)

Abstract

The functional aspects of protein carboxylmethylation in eucaryotic cells have remained enigmatic. Some of the major issues which obscure the possible role of this enzyme are 1) the nature and specificity of relevant in vivo protein substrates; 2) the stoichiometry of protein carboxylmethylation and 3) the rapid hydrolysis of carboxylmethylesters under conditions of neutral and basic pH (Billingsley and Lovenberg, 1985). Thus, two major schools of thought have arisen which attempt to address these issues-the functionalists, who look for revelant substrates which may be regulated by rapid carboxylmethylation, and the structuralists, who suggest that protein carboxylmethylation recognizes and/or repairs either reacemized aspartyl (Terwilliger and Clarke, 1981; McFadden and Clarke, 1982; Murray and Clarke, 1984) or beta isopeptide links (Aswad, 1984; O’Connor, et al., 1984) in a wide range of substrates. We will present evidence which suggests a possible functional role for protein-0-carboxylmethyltransferase (PCM; E.C.2.1.1.24) in nervous tissue based on the following findings.

Keywords

Dopamine Release Bovine Brain Striatal Slice Calmodulin Binding Protein Brain Cytosol 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Aswad, D.W. and Deight, E.A. (1983) J. Neurochem. 40, 1718–1726.PubMedCrossRefGoogle Scholar
  2. Aswad, D.W. (1984) J. Biol. Chem. 259, 10714–10721.PubMedGoogle Scholar
  3. Bradford, M.G. (1976) Analyt. Biochem. 42, 248–254.CrossRefGoogle Scholar
  4. Bannon, M.J., Michaud, R.L., and Roth, R.H. (1981) Mol. Pharmacol. 19, 270–275.PubMedGoogle Scholar
  5. Billingsley, M.L., Kuhn, D.M., Velletri, P.A., Kincaid, R.L., and Lovenberg, W. (1984) J. Biol. Chem. 259, 6630–6635.PubMedGoogle Scholar
  6. Billingsley, M.L., and Lovenberg, W. (1985) Neurochem. Int. (in press).Google Scholar
  7. Billingsley, M.L., Kim, S., and Kuhn, D.M. (1985a) Neuroscience 15, 159–171.PubMedCrossRefGoogle Scholar
  8. Billingsley, M.L., and Balaban, C.D. (1985) Brain Res. (in press).Google Scholar
  9. Billingsley, M.L., Kincaid, R.L., and Kuhn, D.M. (1985b) Proc. Natl. Acad. Sci. USA (in press).Google Scholar
  10. Gagnon, C. (1983) Can. J. Biochem. Cell Biol., 61, 921–926.PubMedCrossRefGoogle Scholar
  11. Kim, S., Nochimson, S., Chin, W., and Paik, W.K. (1978) Analyt. Biochem. 84, 415–422.PubMedCrossRefGoogle Scholar
  12. Kincaid, R.L., and Vaughan, M. (1979) Proc. Natl. Acad. Sci. USA, 76, 4903–4907.PubMedCrossRefGoogle Scholar
  13. Kincaid, R.L., Manganiello, V.C., Odya, C.E., Osbourne, J.C. Jr., Sitth-Coleman, I.E., Daniello, M.A., and Vaughan, M. (1984) J. Biol. Chem. 259, 5150–5166.Google Scholar
  14. Kincaid, R.L., Balaban, C.D., and Billingsley, M.L. (1985) Fed. Proc. 44, 697.Google Scholar
  15. Klee, C.B., Crouch, T.H., and Krinks, M.H. (1979) Proc. Natl. Acad. Sci. USA 76, 6270–6273.PubMedCrossRefGoogle Scholar
  16. McFadden, P.N., and Clarke, S. (1982) Proc. Natl. Acad. Sci. USA, 79, 2460–2464.PubMedCrossRefGoogle Scholar
  17. Murray, E.D., and Clarke, S. (1984) J. Biol. Chem., 259, 10722–10732.PubMedGoogle Scholar
  18. O’Connor, C.M., Aswad, D.W., and Clarke, S.E. (1984) Proc. Natl. Acad. Sci. USA Google Scholar
  19. Pallen, C.J., and Wang, J.H. (1983) J. Biol. Chem. 258, 8550–8553.PubMedGoogle Scholar
  20. Stewart, A.A., Ingebritsen, T.S., Manalan, A., Klee, C.B., and Cohen, P. (1982) FEBS Lett. 137, 80–84.PubMedCrossRefGoogle Scholar
  21. Terwilliger, T.C., and Clarke, S. (1981) J. Biol. Chem. 256, 3067–3076.PubMedGoogle Scholar
  22. Towbin, H., Staehlin, T. and Gordon, J. (1979) Proc. Natl. Acad. Sci. USA, 76, 4350–4354.PubMedCrossRefGoogle Scholar
  23. Wolf, M.E., and Roth, R.H. (1985) J. Neurochem. 44, 291–298.PubMedCrossRefGoogle Scholar

Copyright information

© The Humana Press Inc. 1986

Authors and Affiliations

  • Melvin L. Billingsley
    • 1
  • Randall L. Kincaid
    • 2
  • Marina E. Wolf
    • 3
  • Robert H. Roth
    • 3
  • Walter Lovenberg
    • 2
  • Carey D. Balaban
    • 1
  • S. Milton
    • 1
  1. 1.Hershey Medical CenterPenn State UniversityHersheyUSA
  2. 2.NHLBINIHBethesdaUSA
  3. 3.Yale University School of MedicineNew HavenUSA

Personalised recommendations