Human cellular src gene product: identification of the myristoylated pp60c-src and blockage of its myristoyl acylation with N-fatty acyl compounds resulted in the suppression of colony formation.
A p60K protein in human colon adenocarcinoma tumor cell lines was identified as a myristoylated pp60c-src by fluorography and radioimmunoprecipitation analysis. Prevention of the myristoylation of pp60c-src was determined with N-fatty acyl glycinal compounds. Of the compounds tested, N-myristoyl glycinal diethylacetal, N-lauroyl glycinal diethylacetal, N-myristoyl glycyl glycinal diethylacetal, and N-myristoyl-4-aminobutyl-aldehyde diethylacetal strongly blocked the myristoylation, but N-decanoyl glycinal diethylacetal and N-palmitoyl glycinal diethylacetal did not. The myristoyl blocking compounds depressed colony formation, cell proliferation, and specific localization to the plasma membrane of pp60c-src. The results taken together suggest that myristoylation of the c-src oncogene product may be very important for tumorigenicity of c-src gene expressed cells.
Shoji
S
S
Department of Biochemistry, Faculty of Pharmaceutical Sciences, Kimamoto University, Japan.
Kurosawa
T
T
Inoue
H
H
Funakoshi
T
T
Kubota
Y
Y
D000079:Acetaldehyde / Q000494:pharmacology*; D000080:Acetals / Q000494:pharmacology*; D000215:Acylation; D000230:Adenocarcinoma / Q000175:diagnosis* / Q000188:drug therapy / Q000648:ultrastructure; D003110:Colonic Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000648:ultrastructure; D005455:Fluorescent Antibody Technique; D006801:Humans; D009226:Myristates / Q000378:metabolism*; D015688:Oncogene Protein pp60(v-src) / Q000032:analysis*; D015531:Radioimmunoprecipitation Assay; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
D000080:Acetals; D009226:Myristates; C057591:N-myristoyl glycinal diethylacetal; D015688:Oncogene Protein pp60(v-src); D000079:Acetaldehyde