Superantigen-induced corticosteroid resistance of human T cells occurs through activation of the mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (MEK-ERK) pathway

2004 ◽  
Vol 114 (5) ◽  
pp. 1059-1069 ◽  
Author(s):  
Ling-bo Li ◽  
Elena Goleva ◽  
Clifton F. Hall ◽  
Liang-Shiou Ou ◽  
Donald Y.M. Leung
Keyword(s):  
T Cells ◽  
Protein Kinase ◽  
Mitogen Activated Protein Kinase ◽  
Erk Pathway ◽  
Extracellular Signal Regulated Kinase ◽  
Corticosteroid Resistance ◽  
Human T Cells ◽  
Extracellular Signal ◽  
Mitogen Activated Protein ◽  
Protein Kinase Kinase

scholarly journals RACK1 Targets the Extracellular Signal-Regulated Kinase/Mitogen-Activated Protein Kinase Pathway To Link Integrin Engagement with Focal Adhesion Disassembly and Cell Motility

2007 ◽  
Vol 27 (23) ◽  
pp. 8296-8305 ◽  
Author(s):  
Tomas Vomastek ◽  
Marcin P. Iwanicki ◽  
Hans-Joerg Schaeffer ◽  
Adel Tarcsafalvi ◽  
J. Thomas Parsons ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Focal Adhesion ◽  
Focal Adhesions ◽  
Mitogen Activated Protein Kinase ◽  
Erk Pathway ◽  
Large Measure ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Mitogen Activated Protein ◽  
Erk Activity

ABSTRACT The extracellular signal-regulated kinase (ERK) cascade is activated in response to a multitude of extracellular signals and converts these signals into a variety of specific biological responses, including cell differentiation, cell movement, cell division, and apoptosis. The specificity of the biological response is likely to be controlled in large measure by the localization of signaling, thus enabling ERK activity to be directed towards specific targets. Here we show that the RACK1 scaffold protein functions specifically in integrin-mediated activation of the mitogen-activated protein kinase/ERK cascade and targets active ERK to focal adhesions. We found that RACK1 associated with the core kinases of the ERK pathway, Raf, MEK, and ERK, and that attenuation of RACK1 expression resulted in a decrease in ERK activity in response to adhesion but not in response to growth factors. RACK1 silencing also caused a reduction of active ERK in focal adhesions, an increase in focal adhesion length, a decreased rate of focal adhesion disassembly, and decreased motility. Our data further suggest that focal adhesion kinase is an upstream activator of the RACK1/ERK pathway. We suggest that RACK1 tethers the ERK pathway core kinases and channels signals from upstream activation by integrins to downstream targets at focal adhesions.

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