Yeung, K. et al. (1999) Suppression of Raf-1 kinase activity and MAP kinase signalling by RKIP. Nature, 401(6749), pp. 173-177. (doi: 10.1038/43686)
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Yeung,_K_-_1999.pdf 243kB |
Publisher's URL: http://dx.doi.org/10.1038/43686
Abstract
Raf-1 phosphorylates and activates MEK-1, a kinase that activates the extracellular signal regulated kinases (ERK). This kinase cascade controls the proliferation and differentiation of different cell types. Here we describe a Raf-1-interacting protein, isolated using a yeast two-hybrid screen. This protein inhibits the phosphorylation and activation of MEK by Raf-1 and is designated RKIP (Raf kinase inhibitor protein). In vitro, RKIP binds to Raf-1, MEK and ERK, but not to Ras. RKIP co-immunoprecipitates with Raf-1 and MEK from cell lysates and colocalizes with Raf-1 when examined by confocal microscopy. RKIP is not a substrate for Raf-1 or MEK, but competitively disrupts the interaction between these kinases. RKIP overexpression interferes with the activation of MEK and ERK, induction of AP-1-dependent reporter genes and transformation elicited by an oncogenically activated Raf-1 kinase. Downregulation of endogenous RKIP by expression of antisense RNA or antibody microinjection induces the activation of MEK-, ERK- and AP-1-dependent transcription. RKIP represents a new class of protein-kinase-inhibitor protein that regulates the activity of the Raf/MEK/ERK module
Item Type: | Articles |
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Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Kolch, Prof Walter |
Authors: | Yeung, K., Seitz, T., Li, S., Janosch, P., McFerran, B., Kaiser, C., Fee, F., Katsanakis, K.D., Rose, D.W., Mischak, H., Sedivy, J.M., and Kolch, W. |
Subjects: | Q Science > QP Physiology |
College/School: | College of Medical Veterinary and Life Sciences |
Journal Name: | Nature |
Publisher: | Nature Publishing Group |
ISSN: | 0028-0836 |
Copyright Holders: | © Copyright Macmillan Magazines Ltd |
First Published: | First published in Nature 401:173-177 |
Publisher Policy: | Reproduced with the permission of the Publisher. |
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