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Suppression of Raf-1 kinase activity and MAP kinase signalling by RKIP

Yeung, K. et al. (1999) Suppression of Raf-1 kinase activity and MAP kinase signalling by RKIP. Nature, 401 (6749). pp. 173-177. ISSN 0028-0836 (doi:10.1038/43686)

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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:Article
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 Publications 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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