Transmembrane signalling associated with ganglioside-induced CD4 modulation.
Ganglioside (GM1) treatment of CD4+ human CEM lymphoma cells stimulated transient phosphoinositide (PI) breakdown, production of inositol phosphates (IP), protein phosphorylation and rapid decrease of CD4 surface expression. A comparison between the actions of GM1 and other agents that affect these signal transduction pathways demonstrated a distinct mechanism for GM1-induced decrease of CD4. GM1 stimulated both phospholipase C activity and protein phosphorylation but had no effect on either cellular cAMP levels or tyrosine kinase activity. Phorbol myristate acetate (PMA) stimulated protein phosphorylation and caused a significant decrease in surface display of CD4. Both of these processes were blocked by pretreating cells with the protein kinase C (PKC) inhibitor H7. These results demonstrate that GM1 stimulates PI turnover and induces a rapid decrease of CD4 surface expression by processes that do not activate adenylate cyclase or tyrosine kinase. They further demonstrate that the mechanism for GM1-induced decrease of CD4 is distinct from the CD4 internalization processes mediated by PKC activity.
Morrison
W J
WJ
Neuroimmunology Research Laboratory, Veterans Administration Medical Center, Portland, OR 97207.
Offner
H
H
Vandenbark
A A
AA
D000262:Adenylyl Cyclases / Q000378:metabolism; D015704:CD4 Antigens / Q000378:metabolism*; D005677:G(M1) Ganglioside / Q000494:pharmacology*; D006801:Humans; D006868:Hydrolysis; D007295:Inositol Phosphates / Q000096:biosynthesis; D010716:Phosphatidylinositols / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology* / Q000502:physiology; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
D015704:CD4 Antigens; D007295:Inositol Phosphates; D010716:Phosphatidylinositols; D005677:G(M1) Ganglioside; D011505:Protein-Tyrosine Kinases; D000262:Adenylyl Cyclases