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Dissociation of phosphoinositide hydrolysis and Ca2+ fluxes from the biological responses of a T-cell hybridoma | J J Sussman
; M Merćep
; T Saito
; R N Germain
; E Bonvini
; J D Ashwell
; | Date: |
18 Aug 1988 | Journal: | Nature, 334 (6183), 625-8 | Abstract: | T lymphocytes can be activated in a variety of ways, including occupancy of the T cell antigen receptor (TCR) complex or cross-linking of certain cell-surface molecules with antibody. Two of the earliest events seen after stimulation are the hydrolysis of phosphatidylinositol bisphosphate to inositol trisphosphate (Ins P3) and 1,2-diacylglycerol (DAG), and an increase in the concentration of intracellular Ca2+ ([Ca2+]i). Later, the cell secretes lymphokines and expresses lymphokine receptors. It has been postulated that the products of the hydrolysis of phosphatidylinositols (Ptd Ins) and fluctuations in [Ca2+]i are critical ’second messengers’, transmitting the signals for the initiation of the later events. We have examined the relationship between these second messengers and the secretion of IL-2 in a murine T cell variant whose missing TCR complex had been reconstituted by gene transfer. Surprisingly, although the IL-2 responses of the transfectant could not be distinguished from the original line expressing the same TCR, Ptd Ins hydrolysis and the increase in [Ca2+]i were substantially reduced or absent in the reconstituted cell. It is therefore possible to dissociate these early biochemical changes from a late biological response, raising questions about the putative causal relationship of these events. | Source: | PubMed, pmid3261394 doi: 10.1038/334625a0 | Services: | Forum | Review | Favorites |
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