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The role of Raf-1 in the regulation of extracellular signal-regulated kinase 2 by the T cell antigen receptor.

作者:Manuel Izquierdo, Sally Bowden, Doreen Ann Cantrell · 发表于:The Journal of Experimental Medicine · 年份:1994 · DOI:10.1084/jem.180.1.401 · 被引用次数:58 · 研究领域:Melanoma and MAPK Pathways、Cancer Mechanisms and Therapy、Protein Kinase Regulation and GTPase Signaling

Triggering of the T cell antigen receptor (TCR) complex activates the serine/threonine kinase Raf-1 whose function is necessary for TCR induction of the interleukin 2 gene. Raf-1 has been identified as a candidate mitogen-activated protein (MAP) kinase kinase kinase (MKKK) and thus has the potential to couple the TCR to the activation of the MAP kinases such as ERK2. In the present study, the role of Raf-1 in ERK2 regulation of ERK2 in T cells has been explored. A constitutively active Raf-1 kinase, v-raf, or a dominant inhibitory Raf-1 mutant were expressed transiently from the pEF BOS vector in Jurkat cells and the effects of these Raf-1 mutants on a coexpressed ERK2 reporter was assessed. The action of the constitutively active Raf-1 was to stimulate the ERK2 kinase, whereas the dominant negative version of Raf-1 inhibited the ERK2 activation induced by triggering of the TCR. These data indicate a role for Raf-1 in the regulation of ERK2 in T cells.