Normal T cells express two T cell antigen receptor populations, one of which is linked to the cytoskeleton via zeta chain and displays a unique activation-dependent phosphorylation pattern.
The TCR couples antigen recognition and the transmission of activation signals. We report the expression of two TCR populations on the surface of T lymphocytes, one of which is linked to the cytoskeleton via the zeta chain. We also demonstrate that assembly of the CD3 subunits with cytoskeleton-associated zeta is necessary for their maximal localization to the cytoskeleton. The potential significance of these two receptor forms is underscored by differences observed in non-activated T cells; while detergent-soluble phosphorylated zeta appears as a 21-kDa protein, phosphorylated cytoskeleton-associated zeta appears as a 16-kDa form. This dichotomous phosphorylation pattern is rigidly maintained following activation, although each of the receptor populations undergoes different activation-dependent modifications: 1) levels of soluble phosphorylated 21-kDa zeta are enhanced, while phosphorylated 16-kDa cytoskeleton-associated zeta exhibits little change; 2) soluble non-phosphorylated 16-kDa zeta translocates to the cytoskeleton; 3) activation-dependent ubiquitinated zeta forms localize to both fractions, albeit with different kinetics. We also show that the protein tyrosine kinase Lck undergoes activation-dependent modifications and translocates to the cytoskeleton. The phosphorylation profiles of the dichotomous TCR populations in both non-activated and activated lymphocytes suggest that each population could regulate distinct cellular functions, possibly by select intermolecular associations.
Caplan
S
S
The Lautenberg Center for General and Tumor Immunology, Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel.
Baniyash
M
M
D000818:Animals; D002451:Cell Compartmentation; D003599:Cytoskeleton / Q000378:metabolism*; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D008213:Lymphocyte Activation; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D046911:Macromolecular Substances; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D017830:Octoxynol / Q000737:chemistry; D010766:Phosphorylation; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry* / Q000378:metabolism*; D015398:Signal Transduction; D012995:Solubility; D013601:T-Lymphocytes / Q000502:physiology*; D019061:src-Family Kinases / Q000378:metabolism
D046911:Macromolecular Substances; D008565:Membrane Proteins; D011948:Receptors, Antigen, T-Cell; C054979:antigen T cell receptor, zeta chain; D017830:Octoxynol; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D019061:src-Family Kinases