T cell receptor tyrosine phosphorylation. Variable coupling for different activating ligands.
We have previously reported (Samelson, L.E., Patel, M.D., Weissman, A.M., Harford, J.B., and Klausner, R.D. (1986) Cell 46, 1083-1090) that T cell activation by antigen is associated with activation of two biochemical pathways. In this scheme two protein kinases are activated by stimulation of the T cell antigen receptor (TCR). These kinases phosphorylate two different chains of the TCR complex. Protein kinase C is responsible for the phosphorylation of the gamma, and, to a lesser extent, the epsilon chains of the receptor on serine residues while the activation of an unidentified tyrosine kinase leads to phosphorylation of the p21 subunit of the receptor on tyrosine residues. In addition to activation by specific antigens, T cells can be functionally activated in vitro by the addition of antibodies that bind either the antigen receptor or the Thy-1 molecule, an entity independent of the receptor. We have used antibodies directed against these molecules and show that they result in the same dual kinase activation observed with antigen stimulation. In addition we have compared the three ligands, antigen, and antibodies directed against the epsilon chain of the TCR or against Thy-1, in terms of how they couple to the two kinase pathways. Activation of phosphatidylinositol breakdown and TCR phosphorylation on serine by all three stimuli are sensitive to cAMP inhibition. In contrast, only antigen-stimulated tyrosine kinase activation is sensitive to cAMP while the two antibody reagents activate the tyrosine kinase in a manner that is entirely insensitive to cAMP inhibition.
D000818:Animals; D007376:Interleukin-2 / Q000378:metabolism; D051379:Mice; D010716:Phosphatidylinositols / Q000378:metabolism; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000187:drug effects / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000378:metabolism; D015375:Receptors, Interleukin-2; D014443:Tyrosine / Q000378:metabolism*
D007376:Interleukin-2; D010716:Phosphatidylinositols; D011948:Receptors, Antigen, T-Cell; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C