Tyrosine kinase-regulated and inositol phosphate-independent Ca2+ elevation and mobilization in T cells

• Published in: The Journal of biological chemistry Vol. 267; no. 10; pp. 7154 - 7159
• Main Authors: Niklinska, B B, Yamada, H, O'Shea, J J, June, C H, Ashwell, J D
• Format: Journal Article
• Language: English
• Published: United States American Society for Biochemistry and Molecular Biology 05.04.1992
• Subjects: Animals; Benzoquinones; Calcium - metabolism; Cations, Divalent; Columbidae; Fluorescent Antibody Technique; Hybridomas; Hydrolysis; Inositol Phosphates - biosynthesis; Inositol Phosphates - metabolism; Lactams, Macrocyclic; Oncogene Protein pp60(v-src) - metabolism; Phosphorylation; Protein-Tyrosine Kinases - metabolism; Quinones - pharmacology; Receptors, Antigen, T-Cell - metabolism; Rifabutin - analogs & derivatives; Signal Transduction; T-Lymphocytes - metabolism; Terpenes - pharmacology; Thapsigargin
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/S0021-9258(19)50551-8

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+.