Abstract |
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.
|
Authors | N Hanai, T Dohi, G A Nores, S Hakomori |
Journal | The Journal of biological chemistry
(J Biol Chem)
Vol. 263
Issue 13
Pg. 6296-301
(May 05 1988)
ISSN: 0021-9258 [Print] United States |
PMID | 2834372
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
|
Chemical References |
- Antibodies, Monoclonal
- G(M3) Ganglioside
- Gangliosides
- de-N-acetylneuraminyllactosylceramide
- ErbB Receptors
- Protein-Tyrosine Kinases
|
Topics |
- Animals
- Antibodies, Monoclonal
- Cell Division
(drug effects)
- Cell Line
- Chromatography, High Pressure Liquid
- Chromatography, Thin Layer
- ErbB Receptors
- G(M3) Ganglioside
(analogs & derivatives, metabolism, pharmacology)
- Gangliosides
(pharmacology)
- Immunosorbent Techniques
- Melanoma
(enzymology)
- Mice
- Promoter Regions, Genetic
- Protein-Tyrosine Kinases
(metabolism)
|