Lipid raft distribution of CD4 depends on its palmitoylation and association with Lck, and evidence for CD4-induced lipid raft aggregation as an additional mechanism to enhance CD3 signaling.
By mutagenesis, we demonstrated that the palmitoylation of the membrane-proximal Cys(396) and Cys(399)of CD4, and the association of CD4 with Lck contribute to the enrichment of CD4 in lipid rafts. Ab cross-linking of CD4 induces an extensive membrane patching on the T cell surface, which is related to lipid raft aggregation. The lipid raft localization of CD4 is critical for CD4 to induce the aggregation of lipid rafts. The localization of CD4 in lipid rafts also correlates to the ability of CD4 to enhance receptor tyrosine phosphorylation. Thus, our data suggest that CD4-induced aggregation of lipid rafts may play an additional role in CD4 signaling besides its adhesion to MHC molecules and association with Lck.
Fragoso
Roben
R
Skirball Institute of Biomedical Research, New York University School of Medicine, New York 10016, USA.
Ren
Dejian
D
Zhang
Xiaoping
X
Su
Michael Wei-Chih
MW
Burakoff
Steven J
SJ
Jin
Yong-Jiu
YJ
D020816:Amino Acid Motifs / Q000235:genetics / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000378:metabolism; D001665:Binding Sites / Q000235:genetics / Q000276:immunology; D017252:CD3 Complex / Q000502:physiology*; D015704:CD4 Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000502:physiology; D016827:CD8 Antigens / Q000235:genetics / Q000378:metabolism; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D003432:Cross-Linking Reagents / Q000378:metabolism; D003545:Cysteine / Q000235:genetics / Q000378:metabolism; D018390:Gene Targeting; D006801:Humans; D019169:Jurkat Cells; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000235:genetics / Q000378:metabolism*; D021962:Membrane Microdomains / Q000235:genetics / Q000378:metabolism*; D016853:Muromonab-CD3 / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D019308:Palmitic Acid / Q000378:metabolism*; D010766:Phosphorylation; D010957:Plasmids / Q000276:immunology / Q000378:metabolism; D017384:Sequence Deletion / Q000276:immunology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens; C431698:CD8alpha antigen; D003432:Cross-Linking Reagents; D016853:Muromonab-CD3; C079851:OKT4A monoclonal antibody; D019308:Palmitic Acid; D014443:Tyrosine; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D003545:Cysteine