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Título: Isolation and characterization of Jurkat-derived signaling-deficient T cell lines
Autores: Majdalawieh, Amin F.
Fecha: 2002
Publicador: McGill University - MCGILL
Fuente:
Tipo: Electronic Thesis or Dissertation
Tema: Biology, Molecular.
Descripción: In this study, we describe the isolation and characterization of a functionally signaling-deficient Galpha16-negative somatic mutant (hereafter referred to clone 43) derived from the wildtype Jurkat T cell line by means of an activation-induced cell death resistance-based selection strategy. The catalytic activity of Lck in abrogated in clone 43 most likely due to a lack of autophosphorylation at the stimulatory site within the kinase domain of Lck, Y394. Based on Galpha16 cDNA sequencing data, the deficiency presented in clone 43 is most likely due to one or two point mutations located at amino acid residues 26 and 300 of the Galpha16 subunit. Importantly, these signaling defects were fully reversed by re-introduction of wildtype Galpha16 version into clone 43. Indeed, our findings are the first of their kind to validate the proposed model by which the Galpha subunit modulates the activity of Src family of protein tyrosine kinases. These studies underscore the integral role played by Galpha 16 in TCR-mediated signaling and offer a powerful genetic tool to strengthen our knowledge about the regulation and function of G proteins in T lymphocytes. We also describe the phenotype of two other signaling-deficient, Jurkat-derived clones, named clone 15 and clone 21. (Abstract shortened by UMI.)
Idioma: en