Review
Cell Research (2008) 18:452-457. doi: 10.1038/cr.2008.43; published online 1 April 2008
Raf kinase inhibitory protein: a signal transduction modulator and metastasis suppressor
Alexey E Granovsky1 and Marsha Rich Rosner1
1Ben May Department for Cancer Research, University of Chicago, 929 East 57th Street, Chicago, IL 60637, USA
Correspondence: Marsha Rich Rosner, m-rosner@uchicago.edu
Abstract
Cells have a multitude of controls to maintain their integrity and prevent random switching from one biological state to another. Raf Kinase Inhibitory Protein (RKIP), a member of the phosphatidylethanolamine binding protein (PEBP) family, is representative of a new class of modulators of signaling cascades that function to maintain the "yin yang" or balance of biological systems. RKIP inhibits MAP kinase (Raf-MEK-ERK), G protein-coupled receptor (GPCR) kinase and NF
B signaling cascades. Because RKIP targets different kinases dependent upon its state of phosphorylation, RKIP also acts to integrate crosstalk initiated by multiple environmental stimuli. Loss or depletion of RKIP results in disruption of the normal cellular stasis and can lead to chromosomal abnormalities and disease states such as cancer. Since RKIP and the PEBP family have been reviewed previously, the goal of this analysis is to provide an update and highlight some of the unique features of RKIP that make it a critical player in the regulation of cellular signaling processes.
Keywords:
Raf Kinase, metastasis, signal transduction, inhibitor
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