T cell antigen receptor ubiquitination is a consequence of receptor-mediated tyrosine kinase activation.
Engagement of the T cell antigen receptor results in both its phosphorylation and its ubiquitination. T cell antigen receptor ubiquitination was evaluated in Jurkat, a well characterized human T leukemia cell line. Treatment of cells with the tyrosine kinase inhibitor herbimycin A resulted in an inhibition of receptor ubiquitination. Consistent with this, pervanadate, which increases cellular tyrosine phosphorylation, enhanced receptor ubiquitination. A requirement for receptor-mediated tyrosine kinase activity for ubiquitination was confirmed in cells lacking the tyrosine kinase p56lck and also in cells that are defective in expression of CD45, a tyrosine phosphatase that regulates the activity of p56lck. The need for tyrosine kinase activation for ubiquitination was not bypassed by directly activating protein kinase C and stimulating endocytosis of receptors. These observations establish ubiquitination of the T cell antigen receptor as a tyrosine kinase-dependent manifestation of transmembrane signaling and suggest a role for tyrosine phosphorylation in the ligand-dependent ubiquitination of mammalian transmembrane receptors.
Cenciarelli
C
C
Laboratory of Immune Cell Biology, Division of Basic Sciences, NCI, National Institutes of Health, Bethesda, Maryland 20892-1152, USA.
Wilhelm
K G
KG
Guo
A
A
Weissman
A M
AM
D002478:Cells, Cultured; D004789:Enzyme Activation; D006801:Humans; D017493:Leukocyte Common Antigens / Q000378:metabolism; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism*; D014452:Ubiquitins / Q000378:metabolism*; D019061:src-Family Kinases / Q000378:metabolism
D011948:Receptors, Antigen, T-Cell; D014452:Ubiquitins; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D019061:src-Family Kinases; D011493:Protein Kinase C; D017493:Leukocyte Common Antigens