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Diminished tyrosine protein kinase activity in T cells unresponsive to TCR stimulation
Author(s) -
Tsygankov Alexander Y.,
Kim Ha W.,
Pratt Joanne C.,
Spana Carl,
Class Kenneth,
Gaulton Glen N.,
Kamoun Malek,
Bolen Joseph B.
Publication year - 1994
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.55.3.289
Subject(s) - t cell receptor , jurkat cells , tyrosine phosphorylation , biology , phosphorylation , tyrosine kinase , cd3 , proto oncogene tyrosine protein kinase src , receptor tyrosine kinase , microbiology and biotechnology , t cell , kinase , tyrosine , signal transduction , antigen , biochemistry , immunology , immune system , cd8
Tyrosine phosphorylation is thought to be one of the earliest steps in antigenic activation of T cells. Three nonreceptor tyrosine kinases, p56 lck , p60 fyn , and ZAP‐70, are known to be involved in T cell receptor (TCR) signaling, albeit their functional roles appear to be different. Whereas p60 fyn and ZAP‐70 are functionally associated with the T cell antigen receptor, p56 lck is essential for TCR signaling without being directly coupled to the TCR. We have studied a mutant variant of the Jurkat T cell line (J32–3.2), in which basal activities of p56 l ck and p60 fyn are 2‐ to 2.5‐fold reduced relative to those in its parental line (J32) while basal activity of ZAP‐70 remains unchanged, and compared responses of J32–3.2 and J32 to TCR stimulation. We have demonstrated that tyrosine phosphorylation following CD3 cross‐linking in J32–3.2 cells was extremely short‐lived and thus insufficient for the induction of subsequent physiological responses. This was at least partially due to the diminished tyrosine kinase activity in these cells. A decrease in the activity of src ‐related kinases was caused primarily by their lower expression, whereas expression of ZAP‐70 was unchanged but its response to CD3 crosslinking was diminished, correlating with the deficient tyrosine phosphorylation of the CD3 ‐chain, recently observed in J32–3.2. These data are consistent with the idea that sir‐related kinases phosphorylate the ‐chain, which in turn recruits ZAP‐70 required to sustain the signal. J. Leukoc. Biol. 55: 289–298; 1994.