The monosialoganglioside GM1 induces internalisation and degradation of the CD4 antigen in U937 cells: evidence for a novel mechanism of CD4 down-modulation in a p56lck-negative cell line, which is independent of protein kinase C activation.
Sialated glycosphingolipids (gangliosides) were recently shown to induce internalisation of the CD4 Ag in lymphoid cells and dissociation of p56lck from CD4 (Repke et al. (1992) J. Immunol. 149, 2585-2591; Saggioro et al. (1993) J. Biol. Chem. 268, 1368-1375). The findings presented in this paper show that GM1 induces internalisation and the eventual degradation of the CD4 Ag also in the monocytic cell line U937. GM1 effects are independent of a possible activation of protein kinase C, as enzyme inhibitors which effectively blocked phorbol esters effects did not prevent GM1-induced CD4 internalisation and degradation. GM1 effects were also independent of a possible action on a CD4 associated kinase activity as we show that U937 cells lack any CD4-associated kinase activity.
Sorio
C
C
Institute of General Pathology, University of Verona, Italy.
Saggioro
D
D
Chieco-Bianchi
L
L
Berton
G
G
D000470:Alkaloids / Q000494:pharmacology; D053119:Benzophenanthridines; D015704:CD4 Antigens / Q000378:metabolism*; D015536:Down-Regulation; D004705:Endocytosis; D004789:Enzyme Activation; D005677:G(M1) Ganglioside / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D010617:Phenanthridines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D019311:Staurosporine; D014407:Tumor Cells, Cultured
D000470:Alkaloids; D053119:Benzophenanthridines; D015704:CD4 Antigens; D010617:Phenanthridines; D011518:Proto-Oncogene Proteins; D005677:G(M1) Ganglioside; C016299:chelerythrine; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D011493:Protein Kinase C; D019311:Staurosporine