Requirement of the serine at residue 329 for lipid raft recruitment of DNAM-1 (CD226)

Int Immunol. 2005 Mar;17(3):217-23. doi: 10.1093/intimm/dxh199. Epub 2005 Jan 31.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Differentiation, T-Lymphocyte / chemistry
  • Antigens, Differentiation, T-Lymphocyte / metabolism*
  • Humans
  • Lymphocyte Function-Associated Antigen-1 / metabolism
  • Membrane Microdomains / metabolism*
  • Phosphorylation
  • Serine / chemistry
  • Serine / metabolism*
  • Signal Transduction


  • Antigens, Differentiation, T-Lymphocyte
  • CD226 antigen
  • Lymphocyte Function-Associated Antigen-1
  • Serine