Protein tyrosine kinase p59fyn is associated with the T cell receptor-CD3 complex in functional human lymphocytes.
The binding of antigen to the multicomponent T cell antigen receptor (TcR)-CD3 complex leads to the activation of several signal transduction pathways which result in T lymphocyte proliferation and lymphokine secretion by molecular mechanisms and catalytic molecules as yet poorly defined. One of the earliest events that follows the triggering of the antigen-specific TcR-CD3 complex is a rapid tyrosine phosphorylation of several intracellular substrates, suggesting stimulation of at least one protein tyrosine kinase (PTK). Since none of the seven TcR-CD3 subunits exhibits a recognizable kinase domain, it seems likely that the receptor complex is associated with an intracellular PTK. p59fyn and the T lymphocyte-specific p56lck are two intracellular, non-receptor, cell membrane-associated PTK of the src family expressed in T lymphocytes. Here, we show by double immunofluorescence microscopy a specific co-distribution of p59fyn, but not p56lck, with antibody-induced TcR or CD3 caps in intact human T lymphocytes. These findings provide direct evidence for a significant association of p59fyn with the TcR-CD3 complex under physiologically relevant conditions in functional T lymphocytes. They suggest that p59fyn is a crucial component of the TcR signal transduction machinery and that one of the earliest consequences of antigen recognition by the TcR is p59fyn-mediated phosphorylation of intracellular substrates on tyrosine residues.
Gassmann
M
M
Department of Biology, Pharmaceutical Research New Technologies, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
Guttinger
M
M
Amrein
K E
KE
Burn
P
P
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis*; D017252:CD3 Complex; D006801:Humans; D051379:Mice; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000032:analysis*; D011518:Proto-Oncogene Proteins / Q000032:analysis* / Q000502:physiology; D051076:Proto-Oncogene Proteins c-fyn; D011948:Receptors, Antigen, T-Cell / Q000032:analysis*; D015398:Signal Transduction; D014443:Tyrosine / Q000378:metabolism
D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D011518:Proto-Oncogene Proteins; D011948:Receptors, Antigen, T-Cell; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; C494957:FYN protein, human; C494960:Fyn protein, mouse; D051076:Proto-Oncogene Proteins c-fyn