Regulación de la expresión génica de cot quinasa y análisis de su papel en la activación de linfocitos
Autor (es)
Ballester Jareño, AliciaDirector (es)
Alemany de la Peña, SusanaEntidad
UAM. Departamento de BioquímicaFecha de edición
1997-11-14Materias
Linfocitos T-Tesis doctorales; Biología y Biomedicina / BiologíaNota
Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Medicina, Departamento de Bioquímica. Fecha de lectura: 14-11-1997Resumen
Tpl-2 is a rat gene that encodes a serinelthreonine protein kinase that can act as a
novel mitogen-activated protein (MAP) kinase kinase kinase. Tpl-2 is activated in
Moloney munne leukemia vims-induced rat T lymphomas, due to a tmncation in the Cterminal region of the protein. Cor is a very closely related gene, if not the human
homologue. The tmncated form of Cot has been shown to have a higher transforming
activity than the nontruncated form. This work shows the existence of three mRNA
species for cot gene (cot 1, cot 2 and cot 3). Besides, we demonstrate that cor gene
expression is under the control of two promoters: P1 for cot 1 and cot 2, and P2 for cot
3. While P2 has a high constitutive activity, P1 is clearly inducible by T cells-initogenic
stimuli. We demonstrate the existence of a novel exon (3a) not defined previously in
the genomic structure of the cot gene. In this work also we show that an increase in
tmncated Cot kinase expression correlates with an increase in 1L2 production in aCD3-
treated Jurkat cells. Truncated Cot expression also cooperates with PHA or phorbol
12.13-dibutyrate (PDBu) and calcium ionophore (A23 187) for IL2 production in Jurkat
cells. Both, the truncated and nontruncated Cot forms increased IL2 transcription
because~theye nhanced. .t ranscription of. -a reporter gene linked to the IL2 promoter. The expression of a dominant negative form of Cot inhibits transcription directe-d by the IL2- prornoter in Jurkat cells stimulated by PDBu and A23 187. Our results indicate that Coi kinase has a role in nuclear NFAT and AP1 activities in T cells. These data suggest a
role of Tpl-2ICot kinase in IL-2 production during T lymphocyte activation and could
also explain its oncogenic activity.
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Google Scholar:Ballester Jareño, Alicia
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