Reduction in Raf Kinase Inhibitor Protein Expression Is Associated with Increased Ras-Extracellular Signal-Regulated Kinase Signaling in Melanoma Cell Lines

2004 ◽  
Vol 64 (15) ◽  
pp. 5186-5192 ◽  
Author(s):  
Marion M. Schuierer ◽  
Frauke Bataille ◽  
Suzanne Hagan ◽  
Walter Kolch ◽  
Anja-Katrin Bosserhoff
Keyword(s):  
Protein Expression ◽  
Cell Lines ◽  
Melanoma Cell ◽  
Kinase Inhibitor ◽  
Inhibitor Protein ◽  
Extracellular Signal Regulated Kinase ◽  
Raf Kinase ◽  
Raf Kinase Inhibitor Protein ◽  
Extracellular Signal ◽  
Melanoma Cell Lines

scholarly journals Mechanism of Suppression of the Raf/MEK/Extracellular Signal-Regulated Kinase Pathway by the Raf Kinase Inhibitor Protein

2000 ◽  
Vol 20 (9) ◽  
pp. 3079-3085 ◽  
Author(s):  
Kam Yeung ◽  
Petra Janosch ◽  
Brian McFerran ◽  
David W. Rose ◽  
Harald Mischak ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Competitive Inhibitor ◽  
Erk Pathway ◽  
Inhibitor Protein ◽  
Extracellular Signal Regulated Kinase ◽  
Raf Kinase ◽  
Binding Domains ◽  
Inhibitory Function ◽  
Raf Kinase Inhibitor Protein ◽  
Extracellular Signal

ABSTRACT We have recently identified the Raf kinase inhibitor protein (RKIP) as a physiological endogenous inhibitor of the Raf-1/MEK/extracellular signal-regulated kinase (ERK) pathway. RKIP interfered with MEK phosphorylation and activation by Raf-1, resulting in the suppression of both Raf-1-induced transformation and AP-1-dependent transcription. Here we report the molecular mechanism of RKIP's inhibitory function. RKIP can form ternary complexes with Raf-1, MEK, and ERK. However, whereas MEK and ERK can simultaneously associate with RKIP, Raf-1 binding to RKIP and that of MEK are mutually exclusive. RKIP is able to dissociate a Raf-1–MEK complex and behaves as a competitive inhibitor of MEK phosphorylation. Mapping of the binding domains showed that MEK and Raf-1 bind to overlapping sites in RKIP, whereas MEK and RKIP associate with different domains in Raf-1, and Raf-1 and RKIP bind to different sites in MEK. Both the Raf-1 and the MEK binding sites in RKIP need to be destroyed in order to relieve RKIP-mediated suppression of the Raf-1/MEK/ERK pathway, indicating that binding of either Raf-1 or MEK is sufficient for inhibition. The properties of RKIP reveal the specific sequestration of interacting components as a novel motif in the cell's repertoire for the regulation of signaling pathways.

scholarly journals Frequent loss of RAF kinase inhibitor protein expression in acute myeloid leukemia

Leukemia ◽  
2012 ◽  
Vol 26 (8) ◽  
pp. 1842-1849 ◽  
Author(s):  
A Zebisch ◽  
A Wölfler ◽  
I Fried ◽  
O Wolf ◽  
K Lind ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Protein Expression ◽  
Myeloid Leukemia ◽  
Kinase Inhibitor ◽  
Inhibitor Protein ◽  
Raf Kinase ◽  
Raf Kinase Inhibitor Protein ◽  
Acute Myeloid

scholarly journals Reduction of Raf kinase inhibitor protein expression by Bcr-Abl contributes to chronic myelogenous leukemia proliferation.

2010 ◽  
Vol 285 (19) ◽  
pp. 14841.2-14841
Author(s):  
Tomonari Takemura ◽  
Satoki Nakamura ◽  
Daisuke Yokota ◽  
Isao Hirano ◽  
Takaaki Ono ◽  
...  
Keyword(s):  
Protein Expression ◽  
Chronic Myelogenous Leukemia ◽  
Kinase Inhibitor ◽  
Myelogenous Leukemia ◽  
Inhibitor Protein ◽  
Raf Kinase ◽  
Raf Kinase Inhibitor Protein

scholarly journals Raf Kinase Inhibitor Protein Expression and Prognostic Value in Soft Tissue Sarcomas

Pathobiology ◽  
2016 ◽  
Vol 83 (1) ◽  
pp. 41-46 ◽  
Author(s):  
Olga Martinho ◽  
Marcelo Campos ◽  
Guilherme Ribeiro ◽  
Valter Penna ◽  
Emílio C. Curcelli ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Protein Expression ◽  
Prognostic Value ◽  
Kinase Inhibitor ◽  
Soft Tissue Sarcomas ◽  
Inhibitor Protein ◽  
Raf Kinase ◽  
Raf Kinase Inhibitor Protein

scholarly journals Reduction of Raf Kinase Inhibitor Protein Expression by Bcr-Abl Contributes to Chronic Myelogenous Leukemia Proliferation

2009 ◽  
Vol 285 (9) ◽  
pp. 6585-6594 ◽  
Author(s):  
Tomonari Takemura ◽  
Satoki Nakamura ◽  
Daisuke Yokota ◽  
Isao Hirano ◽  
Takaaki Ono ◽  
...  
Keyword(s):  
Protein Expression ◽  
Chronic Myelogenous Leukemia ◽  
Kinase Inhibitor ◽  
Myelogenous Leukemia ◽  
Inhibitor Protein ◽  
Raf Kinase ◽  
Raf Kinase Inhibitor Protein
Sign in / Sign up

Export Citation Format

Share Document