RESUMEN
The Tpl-2 protein serine/threonine kinase was originally identified, in a C-terminally deleted form, as the product of an oncogene associated with the progression of Moloney murine leukemia virus-induced T cell lymphomas in rats. The kinase domain of Tpl-2 is homologous to the Saccharomyces cerevisiae gene product, STE11, which encodes a MAP kinase kinase kinase. This suggested that Tpl-2 might have a similar activity. Consistent with this hypothesis, immunoprecipitated Tpl-2 and Tpl-2deltaC (a C-terminally truncated mutant) phosphorylated and activated recombinant fusion proteins of the mammalian MAP kinase kinases, MEK-1 and SEK-1, in vitro. Furthermore, transfection of Tpl-2 into COS-1 cells or Jurkat T cells. markedly activated the MAP kinases, ERK-1 and SAP kinase (JNK), which are substrates for MEK-1 and SEK-1, respectively. Tpl-2, therefore, is a MAP kinase kinase kinase which can activate two MAP kinase pathways. After Raf and Mos, Tpl-2 is the third serine/threonine oncoprotein kinase that has been shown to function as a direct activator of MEK-1.
Asunto(s)
Proteínas Fetales/metabolismo , MAP Quinasa Quinasa 4 , Quinasas Quinasa Quinasa PAM , Quinasas de Proteína Quinasa Activadas por Mitógenos , Proteínas Quinasas Activadas por Mitógenos , Proteínas Quinasas/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Tirosina Quinasas/metabolismo , Proteínas Tirosina Quinasas Receptoras/metabolismo , Animales , Secuencia de Bases , Proteínas Quinasas Dependientes de Calcio-Calmodulina/metabolismo , Células Cultivadas , Chlorocebus aethiops , Cartilla de ADN/química , Activación Enzimática , Humanos , MAP Quinasa Quinasa 1 , Proteína Quinasa 3 Activada por Mitógenos , Datos de Secuencia Molecular , Fosforilación , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Proto-Oncogénicas c-raf , Proteínas Proto-Oncogénicas p21(ras)/metabolismo , Receptor EphA4 , Transducción de Señal , Linfocitos TRESUMEN
The role of protein kinase C (PKC) in the signaling mechanism that stimulates the release of mediators from rat mast cells, for which the RBL-2H3 cell line is a model, is at present unresolved. Current evidence suggests that PKC activation alone is an insufficient stimulus, although it can modulate mast cell exocytosis induced by other agents. In this article we characterize a variant of the RBL-2H3 cell line that has a reduced capacity for mediator secretion in response to an IgE-mediated antigen-induced stimulation. The outcome of our study suggests that at least two PKC isotypes are active in RBL-2H3 cells, and affect the positive and negative modulation of the secretory response.