A novel ganglioside, de-N-acetyl-GM3 (II3NeuNH2LacCer), acting as a strong promoter for epidermal growth factor receptor kinase and as a stimulator for cell growth.
A novel ganglioside, de-N-acetyl-GM3 (neuraminyllactosylceramide, II3NeuNH2LacCer), was found in the monosialoganglioside fraction of A431 cells and B16 melanoma cells by high-performance liquid chromatography, thin-layer chromatography, and immunoblotting with its specific monoclonal antibody DH5. This novel type of membrane ganglioside strongly enhanced the kinase activity associated with the epidermal growth factor (EGF) receptor, and it showed 32, 35, and 12% growth stimulation as compared with control cultures of A431, Swiss 3T3, and B16 melanoma cells, respectively. Exogenously added de-N-acetyl-GM3 did not alter the affinity of EGF binding to its receptor. These properties of de-N-acetyl-GM3 are in striking contrast to those of GM3 and its lyso derivative (lyso-GM3) which were previously shown to inhibit EGF receptor kinase activity and to inhibit growth in the same cells. These data indicate that de-N-acetylation at the sialic acid moiety of GM3 ganglioside is an important mechanism for modulation of EGF-dependent cell growth. The mechanism is antagonistic to that of GM3-dependent modulation of receptor function.
Hanai
N
N
Department of Biochemical Oncology, Fred Hutchinson Cancer Center, Seattle, Washington.
Dohi
T
T
Nores
G A
GA
Hakomori
S
S
D000818:Animals; D000911:Antibodies, Monoclonal; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D066246:ErbB Receptors; D005679:G(M3) Ganglioside / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D005732:Gangliosides / Q000494:pharmacology*; D007163:Immunosorbent Techniques; D008545:Melanoma / Q000201:enzymology; D051379:Mice; D011401:Promoter Regions, Genetic; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D005679:G(M3) Ganglioside; D005732:Gangliosides; C055763:de-N-acetylneuraminyllactosylceramide; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases