Differential Effects of a Mitogen-Activated Protein Kinase Kinase Inhibitor on Human Neutrophil Responses to Chemotactic Factors

1997 ◽  
Vol 232 (2) ◽  
pp. 474-477 ◽  
Author(s):  
Mitsuyuki Kuroki ◽  
Joseph T. O'Flaherty
Keyword(s):  
Protein Kinase ◽  
Human Neutrophil ◽  
Kinase Inhibitor ◽  
Mitogen Activated Protein Kinase ◽  
Differential Effects ◽  
Mitogen Activated Protein ◽  
Chemotactic Factors ◽  
Protein Kinase Kinase

scholarly journals Activity of the oral mitogen-activated protein kinase kinase inhibitor trametinib inRAS-mutant relapsed or refractory myeloid malignancies

Cancer ◽  
2016 ◽  
Vol 122 (12) ◽  
pp. 1871-1879 ◽  
Author(s):  
Gautam Borthakur ◽  
Leslie Popplewell ◽  
Michael Boyiadzis ◽  
James Foran ◽  
Uwe Platzbecker ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Kinase Inhibitor ◽  
Mitogen Activated Protein Kinase ◽  
Myeloid Malignancies ◽  
Mitogen Activated Protein ◽  
Protein Kinase Kinase

scholarly journals Mitogen-activated protein kinase mediates erythropoietin-induced phosphorylation of the TAL1/SCL transcription factor in murine proerythroblasts

1999 ◽  
Vol 343 (3) ◽  
pp. 615-620 ◽  
Author(s):  
Tong TANG ◽  
K. S. Srinivasa PRASAD ◽  
Mark J. KOURY ◽  
Stephen J. BRANDT
Keyword(s):  
Transcription Factor ◽  
Protein Kinase ◽  
Kinase Inhibitor ◽  
Erythroid Differentiation ◽  
Signalling Pathway ◽  
Mitogen Activated Protein Kinase ◽  
Friend Virus ◽  
Phosphatidylinositol 3 Kinase ◽  
Mitogen Activated Protein ◽  
Protein Kinase Kinase

Ectopic expression of the basic helix-loop-helix transcription factor TAL1 (or SCL) is the most frequent gain-of-function mutation in T-cell acute lymphoblastic leukaemia. Gene-knockout studies in mice have demonstrated that TAL1 is required for embryonic and adult haematopoiesis, and considerable evidence suggests it also has important functions in terminal erythroid differentiation. We reported previously that TAL1 phosphorylation is stimulated by erythropoietin in splenic proerythroblasts isolated from mice infected with the anaemia-inducing strain of Friend virus and show here the signalling pathway responsible. Erythropoietin was found to stimulate nuclear mitogen-activated protein kinase activity in addition to TAL1 protein phosphorylation, both of which were quantitatively inhibited by the mitogen-activated protein kinase kinase inhibitor PD 098059 and the phosphatidylinositol 3-kinase inhibitor wortmannin. Tryptic phosphopeptide analysis of radiolabelled TAL1 immunoprecipitated from nuclear extracts of Friend virus-induced proerythroblasts revealed that phosphorylation of Ser122, shown previously to be a substrate for the mitogen-activated protein kinase ERK1 (extracellular signal-regulated protein kinase) in vitro, was specifically, although not exclusively, increased by erythropoietin and inhibited by wortmannin and PD 098059. These results are consistent with an erythropoietin-stimulated signalling pathway in which there is direct activation of a mitogen-activated protein kinase kinase by phosphatidylinositol 3-kinase and identify TAL1 as one of its nuclear targets. These data suggest, in addition, a specific mechanism by which the principal regulator of erythroid differentiation could enhance TAL1 function, in addition to increasing its expression.

Sign in / Sign up

Export Citation Format

Share Document