Phosphorylation of human N-myristoyltransferase by N-myristoylated SRC family tyrosine kinase members

Biochem Biophys Res Commun. 2001 Oct 19;288(1):233-9. doi: 10.1006/bbrc.2001.5758.

Abstract

N-Myristoyltransferase (NMT) is an essential eukaryotic enzyme that catalyzes the cotranslational and/or posttranslational transfer of myristate to the amino terminal glycine residue of a number of important proteins especially the non-receptor tyrosine kinases whose activity is important for tumorigenesis. Human NMT was found to be phosphorylated by non-receptor tyrosine kinase family members of Lyn, Fyn and Lck and dephosphorylated by the Ca(2+)/calmodulin-dependent protein phosphatase, calcineurin. Deletion of 149 amino acids from the N-terminal end resulted in the absence of phosphorylation suggesting that the phosphorylation sites are located in the N-terminal end of NMT. Furthermore, a site-directed mutagenesis study indicated that substitution of tyrosine 100 with phenylalanine served NMT as a poor substrate for the Lyn kinase. A synthetic peptide corresponding to the amino-terminal region encompassing tyrosine 100 of NMT served as a good substrate for the Lyn and Fyn kinases. Our studies also indicated that NMT was found to interact with Lyn through its N-terminal end in a phosphorylation-dependent manner. This is the first study demonstrating the cross-talk between NMT and their myristoylated protein substrates in signaling pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyltransferases / chemistry
  • Acyltransferases / genetics
  • Acyltransferases / metabolism*
  • Calcineurin / metabolism
  • Humans
  • Kinetics
  • Mutagenesis, Site-Directed
  • Myristic Acid / metabolism*
  • Peptides / metabolism
  • Phosphorylation
  • Phosphotyrosine / metabolism
  • src-Family Kinases / physiology*

Substances

  • Peptides
  • Myristic Acid
  • Phosphotyrosine
  • Acyltransferases
  • glycylpeptide N-tetradecanoyltransferase
  • lyn protein-tyrosine kinase
  • src-Family Kinases
  • Calcineurin