Phosphorylation of human N-myristoyltransferase by N-myristoylated SRC family tyrosine kinase members.
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.
Rajala
R V
RV
Department of Pathology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
Datla
R S
RS
Carlsen
S A
SA
Anderson
D H
DH
Qi
Z
Z
Wang
J H
JH
Sharma
R K
RK
D000217:Acyltransferases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019703:Calcineurin / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D016297:Mutagenesis, Site-Directed; D019814:Myristic Acid / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D019061:src-Family Kinases / Q000502:physiology*
D010455:Peptides; D019814:Myristic Acid; D019000:Phosphotyrosine; D000217:Acyltransferases; C050480:glycylpeptide N-tetradecanoyltransferase; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases; D019703:Calcineurin