scholarly journals Extracellular Signal-regulated Kinase/90-kDa Ribosomal S6 Kinase/Nuclear Factor-κB Pathway Mediates Phorbol 12-Myristate 13-Acetate-induced Megakaryocytic Differentiation of K562 Cells

2001 ◽  
Vol 276 (16) ◽  
pp. 13186-13191 ◽  
Author(s):  
Kwang-Woon Kim ◽  
Sun-Hee Kim ◽  
Eun-Yup Lee ◽  
Nam Deuk Kim ◽  
Ho-Sung Kang ◽  
...  
Keyword(s):  
K562 Cells ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
S6 Kinase ◽  
Megakaryocytic Differentiation ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Ribosomal S6 Kinase

scholarly journals mTORC2 Is Involved in the Induction of RSK Phosphorylation by Serum or Nutrient Starvation

Cells ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 1567
Author(s):  
Po-Chien Chou ◽  
Swati Rajput ◽  
Xiaoyun Zhao ◽  
Chadni Patel ◽  
Danielle Albaciete ◽  
...  
Keyword(s):  
Protein Kinases ◽  
Mitogen Activated Protein Kinase ◽  
S6 Kinase ◽  
Agc Kinases ◽  
Extracellular Signal Regulated Kinase ◽  
Mechanistic Target Of Rapamycin ◽  
Extracellular Signal ◽  
Mitogen Activated Protein ◽  
Inhibition Of Glycolysis ◽  
Ribosomal S6 Kinase

Cells adjust to nutrient fluctuations to restore metabolic homeostasis. The mechanistic target of rapamycin (mTOR) complex 2 responds to nutrient levels and growth signals to phosphorylate protein kinases belonging to the AGC (Protein Kinases A,G,C) family such as Akt and PKC. Phosphorylation of these AGC kinases at their conserved hydrophobic motif (HM) site by mTORC2 enhances their activation and mediates the functions of mTORC2 in cell growth and metabolism. Another AGC kinase family member that is known to undergo increased phosphorylation at the homologous HM site (Ser380) is the p90 ribosomal S6 kinase (RSK). Phosphorylation at Ser380 is facilitated by the activation of the mitogen-activated protein kinase/extracellular signal regulated kinase (MAPK/ERK) in response to growth factor stimulation. Here, we demonstrate that optimal phosphorylation of RSK at this site requires an intact mTORC2. We also found that RSK is robustly phosphorylated at Ser380 upon nutrient withdrawal or inhibition of glycolysis, conditions that increase mTORC2 activation. However, pharmacological inhibition of mTOR did not abolish RSK phosphorylation at Ser380, indicating that mTOR catalytic activity is not required for this phosphorylation. Since RSK and SIN1β colocalize at the membrane during serum restimulation and acute glutamine withdrawal, mTORC2 could act as a scaffold to enhance RSK HM site phosphorylation. Among the known RSK substrates, the CCTβ subunit of the chaperonin containing TCP-1 (CCT) complex had defective phosphorylation in the absence of mTORC2. Our findings indicate that the mTORC2-mediated phosphorylation of the RSK HM site could confer RSK substrate specificity and reveal that RSK responds to nutrient fluctuations.

scholarly journals Recruitment of the Extracellular Signal-Regulated Kinase/Ribosomal S6 Kinase Signaling Pathway to the NFATc4 Transcription Activation Complex

2005 ◽  
Vol 25 (3) ◽  
pp. 907-920 ◽  
Author(s):  
Teddy T. C. Yang ◽  
Qiufang Xiong ◽  
Isabella A. Graef ◽  
Gerald R. Crabtree ◽  
Chi-Wing Chow
Keyword(s):  
Gene Expression ◽  
Map Kinase ◽  
Signaling Pathway ◽  
Protein Kinases ◽  
Transcription Activation ◽  
S6 Kinase ◽  
Dna Transcription ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Ribosomal S6 Kinase

ABSTRACT Integration of protein kinases into transcription activation complexes influences the magnitude of gene expression. The nuclear factor of activated T cells (NFAT) group of proteins are critical transcription factors that direct gene expression in immune and nonimmune cells. A balance of phosphotransferase activity is necessary for optimal NFAT activation. Activation of NFAT requires dephosphorylation by the calcium-mediated calcineurin phosphatase to promote NFAT nuclear accumulation, and the Ras-activated extracellular signal-regulated kinase (ERK) mitogen-activated protein (MAP) kinase, which targets NFAT partners, to potentiate transcription. Whether protein kinases operate on NFAT and contribute positively to transcription activation is not clear. Here, we coupled DNA affinity isolation with in-gel kinase assays to avidly pull down the activated NFAT and identify its associated protein kinases. We demonstrate that p90 ribosomal S6 kinase (RSK) is recruited to the NFAT-DNA transcription complex upon activation. The formation of RSK-NFATc4-DNA transcription complex is also apparent upon adipogenesis. Bound RSK phosphorylates Ser676 and potentiates NFATc4 DNA binding by escalating NFAT-DNA association. Ser676 is also targeted by the ERK MAP kinase, which interacts with NFAT at a distinct region than RSK. Thus, integration of the ERK/RSK signaling pathway provides a mechanism to modulate NFATc4 transcription activity.

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