Isolation of mutant T lymphocytes with defects in capacitative calcium entry

Autor: Leonard A. Herzenberg, Christopher M. Fanger, Andrew T. Serafini, Gerald R. Crabtree, Richard S. Lewis, Neil A. Clipstone, Steve Flering, Richard J. Bram
Rok vydání: 1995
Předmět:
Zdroj: Immunity. 3:239-250
ISSN: 1074-7613
DOI: 10.1016/1074-7613(95)90093-4
Popis: Calcium and calcium-binding proteins play important roles in the signaling cascade leading from the initial engagement of TCRs on T cells to the fully activated state. To undertake a molecular dissection of this cascade, we first isolated a Jurkat T cell line derivative containing the NF-AT promoter element driving transcription of the diphtheria toxin A chain gene ( dipA ), resulting in rapid cell death. Selecting viable cells that fail to activate NF-AT-dependent transcription, we isolated two independent cell lines possessing defects in capacitative Ca 2+ entry. NF-AT-dependent transcription can be restored in these cells by expression of a constitutively active calcineurin, but not by overexpression of the Ca 2+ regulatory protein CAML, which can normally replace the Ca 2+ signal. The defect in these cell lines probably lies between CAML and calcineurin in the T cell activation cascade.
Databáze: OpenAIRE