scholarly journals Inhibition of extracellular signal-regulated kinase activity by sorafenib increases sensitivity to DNR in K562 cells

2013 ◽  
Vol 29 (5) ◽  
pp. 1895-1901 ◽  
Author(s):  
RUO-ZHI XIAO ◽  
CHENG-MING HE ◽  
MU-JUN XIONG ◽  
XING-XING RUAN ◽  
LI-LIN WANG ◽  
...  
Keyword(s):  
Kinase Activity ◽  
K562 Cells ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal

scholarly journals Multiregion Quantification of Extracellular Signal-regulated Kinase Activity in Renal Cell Carcinoma

2020 ◽  
Vol 3 (3) ◽  
pp. 360-364 ◽  
Author(s):  
Christian R. Hoerner ◽  
Rustin Massoudi ◽  
Thomas J. Metzner ◽  
Laurel Stell ◽  
Jennifer J. O’Rourke ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Kinase Activity ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal

scholarly journals Feedforward regulation of mRNA stability by prolonged extracellular signal-regulated kinase activity

FEBS Journal ◽  
2015 ◽  
Vol 282 (4) ◽  
pp. 613-629 ◽  
Author(s):  
Takeshi Nagashima ◽  
Norihiko Inoue ◽  
Noriko Yumoto ◽  
Yuko Saeki ◽  
Shigeyuki Magi ◽  
...  
Keyword(s):  
Mrna Stability ◽  
Kinase Activity ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal

scholarly journals Impact of Feedback Phosphorylation and Raf Heterodimerization on Normal and Mutant B-Raf Signaling

2009 ◽  
Vol 30 (3) ◽  
pp. 806-819 ◽  
Author(s):  
Daniel A. Ritt ◽  
Daniel M. Monson ◽  
Suzanne I. Specht ◽  
Deborah K. Morrison
Keyword(s):  
Binding Site ◽  
Developmental Disorders ◽  
Kinase Activity ◽  
Dominant Negative ◽  
Prolyl Isomerase ◽  
Ras Pathway ◽  
Extracellular Signal Regulated Kinase ◽  
Raf Kinase ◽  
Extracellular Signal ◽  
Signaling Activity

ABSTRACT The B-Raf kinase is a Ras pathway effector activated by mutation in numerous human cancers and certain developmental disorders. Here we report that normal and oncogenic B-Raf proteins are subject to a regulatory cycle of extracellular signal-regulated kinase (ERK)-dependent feedback phosphorylation, followed by PP2A- and Pin1-dependent dephosphorylation/recycling. We identify four S/TP sites of B-Raf phosphorylated by activated ERK and find that feedback phosphorylation of B-Raf inhibits binding to activated Ras and disrupts heterodimerization with C-Raf, which is dependent on the B-Raf pS729/14-3-3 binding site. Moreover, we find that events influencing Raf heterodimerization can alter the transforming potential of oncogenic B-Raf proteins possessing intermediate or impaired kinase activity but have no significant effect on proteins with high kinase activity, such as V600E B-Raf. Mutation of the feedback sites or overexpression of the Pin1 prolyl-isomerase, which facilitates B-Raf dephosphorylation/recycling, resulted in increased transformation, whereas mutation of the S729/14-3-3 binding site or expression of dominant negative Pin1 reduced transformation. Mutation of each feedback site caused increased transformation and correlated with enhanced heterodimerization and activation of C-Raf. Finally, we find that B-Raf and C-Raf proteins containing mutations identified in certain developmental disorders constitutively heterodimerize and that their signaling activity can also be modulated by feedback phosphorylation.

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