Requirement of the serine at residue 329 for lipid raft recruitment of DNAM-1 (CD226).
Upon antigen recognition by the TCR, leukocyte function-associated antigen-1 (LFA-1) physically associates with the leukocyte adhesion molecule DNAM-1 (CD226), for which the serine phosphorylation at residue 329 (S329) of DNAM-1 plays a critical role. The TCR-mediated signal also induces the formation of the immunological synapse (IS), in which lipid raft-associated molecules, including LFA-1, DNAM-1, protein kinase C, Fyn and others, are recruited, resulting in efficient signal transduction for T cell activation. However, the molecular mechanisms of lipid raft recruitment of many associated molecules have remained unclear. Here, we demonstrate that, while both wild-type (WT) and mutant DNAM-1 at S329 were polarized at the IS, the WT, but not mutant, DNAM-1 associated with lipid rafts at the peripheral supra-molecular activation clusters. We also demonstrate that the association of DNAM-1 with lipid rafts was necessary for the tyrosine phosphorylation of DNAM-1, which is essential for LFA-1-mediated co-stimulatory signaling for naive T cell proliferation and differentiation.
Shirakawa
Jun
J
Department of Immunology, Institute of Basic Medical Sciences, Graduate School of Comprehensive Human Sciences and Center for TARA, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
Shibuya
Kazuko
K
Shibuya
Akira
A
D000945:Antigens, Differentiation, T-Lymphocyte / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D021962:Membrane Microdomains / Q000378:metabolism*; D010766:Phosphorylation; D012694:Serine / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction; D000098862:T Lineage-Specific Activation Antigen 1
D000945:Antigens, Differentiation, T-Lymphocyte; D000098862:T Lineage-Specific Activation Antigen 1; D016169:Lymphocyte Function-Associated Antigen-1; D012694:Serine