Tyrosine kinase-regulated and inositol phosphate-independent Ca2+ elevation and mobilization in T cells.
Perturbation of the T cell antigen-specific receptor leads to a series of signaling events that includes a rapid increase in phosphoinositide hydrolysis, intracellular Ca2+, and tyrosine phosphorylation. We have examined the function of tyrosine phosphorylation in isolation by introducing the v-src tyrosine kinase into a T cell hybridoma. T cell receptor-mediated increases in phosphoinositide hydrolysis and, in particular the generation of inositol 1,4,5-trisphosphate, were comparable between v-src+ and v-src- cells. Unexpectedly, the v-src+ cells exhibited spontaneously elevated intracellular Ca2+ and exaggerated Ca2+ increases when stimulated via the T cell receptor. The enhanced Ca2+ response was not due to tyrosine phosphorylation of the T cell receptor itself, since the phenotype was evident in T cell receptor zeta chain-/v-src+ cells as well. These results demonstrate that an active protein tyrosine kinase can markedly affect intracellular Ca2+ handling by a process independent of inositol 1,4,5-trisphosphate production and T cell receptor tyrosine phosphorylation and raise the possibility that tyrosine kinases may directly regulate T cell receptor-mediated changes in intracellular Ca2+.
Niklinska
B B
BB
Immune Cell Biology Section, National Institutes of Health, Bethesda, Maryland 20892.
Yamada
H
H
O'Shea
J J
JJ
June
C H
CH
Ashwell
J D
JD
D000818:Animals; D016227:Benzoquinones; D002118:Calcium / Q000378:metabolism*; D002413:Cations, Divalent; D010856:Columbidae; D005455:Fluorescent Antibody Technique; D006825:Hybridomas; D006868:Hydrolysis; D007295:Inositol Phosphates / Q000096:biosynthesis / Q000378:metabolism*; D047029:Lactams, Macrocyclic; D015688:Oncogene Protein pp60(v-src) / Q000378:metabolism; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011809:Quinones / Q000494:pharmacology; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D017828:Rifabutin / Q000031:analogs & derivatives; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism*; D013729:Terpenes / Q000494:pharmacology; D019284:Thapsigargin
D016227:Benzoquinones; D002413:Cations, Divalent; D007295:Inositol Phosphates; D047029:Lactams, Macrocyclic; D011809:Quinones; D011948:Receptors, Antigen, T-Cell; D013729:Terpenes; D017828:Rifabutin; D019284:Thapsigargin; C020754:herbimycin; D011505:Protein-Tyrosine Kinases; D015688:Oncogene Protein pp60(v-src); D002118:Calcium