Amino acids stimulate phosphorylation of p70 S6k and organization of rat adipocytes into multicellular clusters

1998 ◽  
Vol 274 (1) ◽  
pp. C206-C213 ◽  
Author(s):  
Heather L. Fox ◽  
Scot R. Kimball ◽  
Leonard S. Jefferson ◽  
Christopher J. Lynch
Keyword(s):  
Amino Acids ◽  
Primary Culture ◽  
Signaling Pathway ◽  
Culture Medium ◽  
Cluster Formation ◽  
S6 Kinase ◽  
Rat Adipocytes ◽  
Ribosomal Protein S6 ◽  
P70 S6k ◽  
Fasted Rats

In previous studies we have shown that rat adipocytes suspended in Matrigel and placed in primary culture migrate through the gel to form multicellular clusters over a 5- to 6-day period. In the present study, phosphorylation of the insulin-regulated 70-kDa ribosomal protein S6 kinase (p70 S6k ) was observed within 30 min of establishment of adipocytes in primary culture. Two inhibitors of the p70 S6k signaling pathway, rapamycin and LY-294002, greatly reduced phosphorylation of p70 S6k and organization of adipocytes into multicellular clusters. Of all the components of the cell culture medium, amino acids, and in particular a subset of neutral amino acids, were found to promote both phosphorylation of p70 S6k and cluster formation. Lowering the concentrations of amino acids in the medium to levels approximating those in plasma of fasted rats decreased both phosphorylation of p70 S6k and cluster formation. Furthermore, stimulation of p70 S6k phosphorylation by amino acids was prevented by either rapamycin or LY-294002. These findings demonstrate that amino acids stimulate the p70 S6k signaling pathway in adipocytes and imply a role for this pathway in multicellular clustering.

Glucose exerts a permissive effect on the regulation of the initiation factor 4E binding protein 4E-BP1

2001 ◽  
Vol 358 (2) ◽  
pp. 497-503 ◽  
Author(s):  
Jigna PATEL ◽  
Xuemin WANG ◽  
Christopher G. PROUD
Keyword(s):  
Amino Acids ◽  
Ribosomal Protein ◽  
Binding Protein ◽  
Mammalian Target Of Rapamycin ◽  
Mrna Translation ◽  
Initiation Factor ◽  
Ribosomal Protein S6 ◽  
P70 S6k ◽  
Effect Of Glucose

The eukaryotic initiation factor 4E (eIF4E) binding protein (4E-BP1) interacts directly with eIF4E and prevents it from forming initiation factor (eIF4F) complexes required for the initiation of cap-dependent mRNA translation. Insulin and other agents induce the phosphorylation of 4E-BP1 at multiple sites, resulting in its release from eIF4E, and this involves signalling through the mammalian target of rapamycin (mTOR). Here we show that d-glucose promotes the ability of insulin to bring about the phosphorylation of 4E-BP1 and the formation of eIF4F complexes. This appears to involve facilitation of the phosphorylation of at least three phosphorylation sites on 4E-BP1, i.e. Thr-36, Thr-45 and Thr-69. Non-metabolizable glucose analogues cannot substitute for d-glucose, but other hexoses can. This suggests that a product of hexose metabolism mediates the permissive effect of glucose. The effect of glucose was concentration-dependent within the range 1–5mM. In contrast with the situation for 4E-BP1, glucose does not allow full activation of the 70kDa ribosomal protein S6 kinase (p70 S6k; another target of mTOR signalling) or phosphorylation, in vivo, of its substrate, ribosomal protein S6. Taken together with earlier data showing that amino acids regulate 4E-BP1 and p70 S6k, the present findings show that 4E-BP1 in particular is regulated in response to the availability of both amino acids and sugars.

Glucose and amino acids modulate translation factor activation by growth factors in PC12 cells

2000 ◽  
Vol 347 (2) ◽  
pp. 399-406 ◽  
Author(s):  
Miranda KLEIJN ◽  
Christopher G. PROUD
Keyword(s):  
Amino Acids ◽  
Protein Synthesis ◽  
Growth Factors ◽  
Pc12 Cells ◽  
Initiation Factor ◽  
S6 Kinase ◽  
Translational Machinery ◽  
Ribosomal Protein S6 ◽  
Eif4f Complex ◽  
Extracellular Regulated Kinase

In PC12 phaeochromocytoma cells, protein synthesis is activated by epidermal and nerve growth factors (EGF and NGF). EGF and NGF also regulate a number of components of the translational machinery in these cells. Here we show that the ability of EGF and NGF to induce the phosphorylation of the 70 kDa ribosomal protein, S6 kinase, and the eukaryotic initiation factor (eIF), 4E-binding protein 1, is dependent upon the presence of amino acids (but not glucose) in the medium. This resembles the regulation of these proteins by insulin, which also requires amino acids. Glucose, but not amino acids, is required for the activation of eIF2B by EGF and NGF. In contrast, EGF and NGF can still activate protein synthesis in the absence of nutrients, suggesting that other regulatory events are important in this. In nutrient-deprived cells, an increase in the phosphorylation of eIF4E, and the assembly of the eIF4F complex by EGF and NGF, coincided with the activation of protein synthesis. In serum-starved cells, activation of protein synthesis, phosphorylation of eIF4E, and formation of the eIF4F complex, were blocked by inhibition of MEK, a component of the extracellular regulated kinase (ERK) signalling pathway. Thus the ERK pathway plays a key role in the regulation of protein synthesis in PC12 cells.

scholarly journals Activation of Downstream mTORC1 Target Ribosomal Protein S6 Kinase (S6K) Can Be Found in a Subgroup of Dutch Patients with Granulomatous Pulmonary Disease

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3545
Author(s):  
Raisa Kraaijvanger ◽  
Kees Seldenrijk ◽  
Els Beijer ◽  
Jan Damen ◽  
Jayne Louise Wilson ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
S6 Kinase ◽  
Downstream Target ◽  
Ribosomal Protein S6 ◽  
Downstream Effector ◽  
Mtorc1 Signaling ◽  
Mtorc1 Pathway ◽  
Granulomatous Disorder ◽  
Granulomatous Diseases ◽  
Mtorc1 Activation

Mechanistic target of rapamycin complex 1 (mTORC1) has been linked to different diseases. The mTORC1 signaling pathway is suggested to play a role in the granuloma formation of sarcoidosis. Recent studies demonstrated conflicting data on mTORC1 activation in patients with sarcoidosis by measuring activation of its downstream target S6 kinase (S6K) with either 33% or 100% of patients. Therefore, the aim of our study was to reevaluate the percentage of S6K activation in sarcoidosis patients in a Dutch cohort. To investigate whether this activation is specific for sarcoid granulomas, we also included Dutch patients with other granulomatous diseases of the lung. The activation of the S6K signaling pathway was evaluated by immunohistochemical staining of its downstream effector phospho-S6 in tissue sections. Active S6K signaling was detected in 32 (43%) of the sarcoidosis patients. Twelve (31%) of the patients with another granulomatous disorder also showed activated S6K signaling, demonstrating that the mTORC1 pathway may be activated in a range for different granulomatous diseases (p = 0.628). Activation of S6K can only be found in a subgroup of patients with sarcoidosis, as well as in patients with other granulomatous pulmonary diseases, such as hypersensitivity pneumonitis or vasculitis. No association between different clinical phenotypes and S6K activation can be found in sarcoidosis.

scholarly journals Control of Paip1-Eukayrotic Translation Initiation Factor 3 Interaction by Amino Acids through S6 Kinase

2014 ◽  
Vol 34 (6) ◽  
pp. 1046-1053 ◽  
Author(s):  
Y. Martineau ◽  
X. Wang ◽  
T. Alain ◽  
E. Petroulakis ◽  
D. Shahbazian ◽  
...  
Keyword(s):  
Amino Acids ◽  
Translation Initiation ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
S6 Kinase ◽  
Translation Initiation Factor 3
Sign in / Sign up

Export Citation Format

Share Document