A Phorbol Ester‐Sensitive Kinase Catalyzes the Phosphorylation of P0 Glycoprotein in Myelin

Kurt R. Brunden, Joseph F. Poduslo

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29 Scopus citations

Abstract

The proposed structural protein of peripheral nerve myelin, P0, has been shown to have several covalent modifications. In addition to being glycosylated, sulfated, and acylated, P0 is phosphorylated, with the intracellular site of this latter addition being in question. By employing nerve injury models that exhibit different levels of P0 biosynthesis in the absence and presence of myelin assembly, we have examined the cellular location of P0 phosphorylation. It is demonstrated that there is comparable P0 phosphorylation in both normal and crush‐injured adult rat sciatic nerves, although the level of biosynthesis of P0 differs between these myelin maintaining and actively myelinating nerve models, respectively. The glycoprotein does not appear to be phosphorylated readily in the transected adult sciatic nerve, a preparation in which P0 biosynthesis is observed but that lacks myelin membrane. These observations suggest that the modification is not associated with the biosynthesis or maturation of P0 in the endoplasmic reticulum or Golgi, but that it instead occurs after myelin assembly. That P0 phosphorylation occurs in the normal nerve even when translation is inhibited by cycloheximide treatment lends further support to this conclusion. P0 is shown to be phosphorylated on one or more serine residues, with all or most of the phosphate group(s) being labile as evidenced by pulse‐chase analysis. Addition of a biologically active phorbol ester, 12‐O‐tetradecanoylphorbol‐13‐acetate or 4β‐phorbol 12, 13‐dibutyrate, substantially increases the extent of [32P]orthophosphate incorporation into the glycoprotein of normal and crushed nerve but not transected nerve. Biologically inactive 4α‐phorbol 12, 13‐didecanoate has no effect on P0 phosphorylation. Similarly, the addition of the cyclic AMP analog 8‐bromo‐cyclic AMP causes no appreciable changes in P0 labeling. These findings indicate that the phorbol ester‐sensitive enzyme, protein kinase C, may be responsible for the phosphorylation of P0 within the myelin membrane.

Original languageEnglish (US)
Pages (from-to)1863-1872
Number of pages10
JournalJournal of neurochemistry
Volume49
Issue number6
DOIs
StatePublished - Dec 1987

Keywords

  • Myelin
  • P glycoprotein
  • Phorbol ester
  • Phosphorylation
  • Protein kinase C

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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