title: Regulation of T-cell receptor signalling by membrane microdomains.
abstract: There is now considerable evidence suggesting that the plasma membrane of mammalian cells is compartmentalized by functional lipid raft microdomains. These structures are assemblies of specialized lipids and proteins and have been implicated in diverse biological functions. Analysis of their protein content using proteomics and other methods revealed enrichment of signalling proteins, suggesting a role for these domains in intracellular signalling. In T lymphocytes, structure/function experiments and complementary pharmacological studies have shown that raft microdomains control the localization and function of proteins which are components of signalling pathways regulated by the T-cell antigen receptor (TCR). Based on these studies, a model for TCR phosphorylation in lipid rafts is presented. However, despite substantial progress in the field, critical questions remain. For example, it is unclear if membrane rafts represent a homogeneous population and if their structure is modified upon TCR stimulation. In the future, proteomics and the parallel development of complementary analytical methods will undoubtedly contribute in further delineating the role of lipid rafts in signal transduction mechanisms.
authors.affiliation: Bone and Joint Research Unit, William Harvey Research Institute, Queen Mary's School of Medicine and Dentistry, Queen Mary's College, London.
authors.forename: Tahir M
authors.initials: TM
authors.lastname: Razzaq
authors.forename: Patricia
authors.initials: P
authors.lastname: Ozegbe
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Jury
authors.forename: Phupinder
authors.initials: P
authors.lastname: Sembi
authors.forename: Nathan M
authors.initials: NM
authors.lastname: Blackwell
authors.forename: Panagiotis S
authors.initials: PS
authors.lastname: Kabouridis
mesh_terms: D006801:Humans; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000378:metabolism; D021962:Membrane Microdomains / Q000276:immunology*; D018448:Models, Immunological; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D015398:Signal Transduction / Q000276:immunology
chemical_list: D011948:Receptors, Antigen, T-Cell; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)