Coupling of GTP-binding to the T cell receptor (TCR) zeta-chain with TCR-mediated signal transduction.
The zeta-subunit of the TCR binds GTP and is a well characterized substrate for a TCR-activated tyrosine kinase. To examine the possible coupling of GTP-binding to zeta with TCR-mediated signal transduction, a mutant (termed J32-3.2) of the T cell line Jurkat (J32) was used. Anti-TCR/CD3 stimulation of the TCR/CD3+ J32-3.2 cells resulted in a weak stimulation of both the phosphatidyl inositol and tyrosine kinase signal transduction pathways, as measured by changes in the level of free intracellular calcium, tyrosine phosphorylation of TCR-zeta, CD3-epsilon and ZAP-70, p56lck, or p59fyn tyrosine kinase activity and IL-2 gene activation. The impaired responsiveness of J32-3.2 cells to anti-TCR/CD3 mAb correlated with a low basal level of GTP-binding to zeta. Furthermore, in J32-3.2 cells TCR activation by antibody ligation caused a weaker increase in GTP-binding to the zeta-chain, as compared with that of wild-type J32 cells, which indicates for the first time that GTP-binding to zeta can be modulated by extracellular signals and suggest that the role of GTP-binding to zeta is to couple the TCR to intracellular signal transduction mechanisms.
Sancho
J
J
Division of Immunology, Beth Israel Hospital, Boston, MA 02215.
Peter
M E
ME
Franco
R
R
Danielian
S
S
Kang
J S
JS
Fagard
R
R
Woods
J
J
Reed
J C
JC
Kamoun
M
M
Terhorst
C
C
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology; D001483:Base Sequence; D018801:CD2 Antigens; D004247:DNA / Q000737:chemistry; D006160:Guanosine Triphosphate / Q000378:metabolism*; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D011485:Protein Binding; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000502:physiology*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000502:physiology; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D018801:CD2 Antigens; D007376:Interleukin-2; D008565:Membrane Proteins; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D011948:Receptors, Antigen, T-Cell; D011971:Receptors, Immunologic; C054979:antigen T cell receptor, zeta chain; D006160:Guanosine Triphosphate; D004247:DNA; D011505:Protein-Tyrosine Kinases