Ras palmitoylation is necessary for N-Ras activation and signal propagation in growth factor signalling

2013 ◽  
Vol 455 (1) ◽  
pp. 131-131 ◽  
Author(s):  
S.-P. Song ◽  
A. Hennig ◽  
K. Schubert ◽  
R. Markwart ◽  
P. Schmidt ◽  
...  
Keyword(s):  
Growth Factor ◽  
Signal Propagation ◽  
Ras Activation ◽  
Growth Factor Signalling

Ras palmitoylation is necessary for N-Ras activation and signal propagation in growth factor signalling

2013 ◽  
Vol 454 (2) ◽  
pp. 323-332 ◽  
Author(s):  
Shu-Ping Song ◽  
Anne Hennig ◽  
Katja Schubert ◽  
Robby Markwart ◽  
Philipp Schmidt ◽  
...  
Keyword(s):  
Growth Factor ◽  
Signal Propagation ◽  
Dominant Negative ◽  
Post Translational Modifications ◽  
Ras Gtpases ◽  
Ras Activation ◽  
Growth Factor Signalling ◽  
Mitogenic Signalling ◽  
Epidermal Growth

Ras GTPases undergo post-translational modifications that govern their subcellular trafficking and localization. In particular, palmitoylation of the Golgi tags N-Ras and H-Ras for exocytotic transport and residency at the PM (plasma membrane). Following depalmitoylation, PM-Ras redistributes to all subcellular membranes causing an accumulation of palmitate-free Ras at endomembranes, including the Golgi and endoplasmic reticulum. Palmitoylation is unanimously regarded as a critical modification at the crossroads of Ras activity and trafficking control, but its precise relevance to native wild-type Ras function in growth factor signalling is unknown. We show in the present study by use of palmitoylation-deficient N-Ras mutants and via the analysis of palmitate content of agonist-activated GTP-loaded N-Ras that only palmitoylated N-Ras becomes activated by agonists. In line with an essential role of palmitoylation in Ras activation, dominant-negative RasS17N loses its blocking potency if rendered devoid of palmitoylation. Live-cell Ras–GTP imaging shows that N-Ras activation proceeds only at the PM, consistent with activated N-Ras–GTP being palmitoylated. Finally, palmitoylation-deficient N-Ras does not sustain EGF (epidermal growth factor) or serum-elicited mitogenic signalling, confirming that palmitoylation is essential for signal transduction by N-Ras. These findings document that N-Ras activation proceeds at the PM and suggest that depalmitoylation, by removing Ras from the PM, may contribute to the shutdown of Ras signalling.

scholarly journals Comparison of growth factor signalling pathway utilisation in cultured normal melanocytes and melanoma cell lines

BMC Cancer ◽  
2012 ◽  
Vol 12 (1) ◽  
Author(s):  
Ji Eun Kim ◽  
Clare Stones ◽  
Wayne R Joseph ◽  
Euphemia Leung ◽  
Graeme J Finlay ◽  
...  
Keyword(s):  
Growth Factor ◽  
Cell Lines ◽  
Melanoma Cell ◽  
Signalling Pathway ◽  
Growth Factor Signalling ◽  
Melanoma Cell Lines ◽  
Growth Factor Signalling Pathway

scholarly journals Growth-factor-dependent phosphorylation of Bim in mitosis

2005 ◽  
Vol 388 (1) ◽  
pp. 185-194 ◽  
Author(s):  
Mário GRÃOS ◽  
Alexandra D. ALMEIDA ◽  
Sukalyan CHATTERJEE
Keyword(s):  
Cell Cycle ◽  
Cell Death ◽  
Growth Factor ◽  
Cell Fate ◽  
Mitogen Activated Protein Kinase ◽  
Dependent Manner ◽  
Post Translational Modification ◽  
Proliferating Cells ◽  
Growth Factor Signalling ◽  
Induced Apoptosis

The regulation of survival and cell death is a key determinant of cell fate. Recent evidence shows that survival and death machineries are regulated along the cell cycle. In the present paper, we show that BimEL [a BH3 (Bcl-2 homology 3)-only member of the Bcl-2 family of proteins; Bim is Bcl-2-interacting mediator of cell death; EL is the extra-long form] is phosphorylated in mitosis. This post-translational modification is dependent on MEK (mitogen-activated protein kinase/extracellular-signal-regulated kinase kinase) and growth factor signalling. Interestingly, FGF (fibroblast growth factor) signalling seems to play an essential role in this process, since, in the presence of serum, inhibition of FGF receptors abrogated phosphorylation of Bim in mitosis. Moreover, we have shown bFGF (basic FGF) to be sufficient to induce phosphorylation of Bim in serum-free conditions in any phase of the cell cycle, and also to significantly rescue cells from serum-deprivation-induced apoptosis. Our results show that, in mitosis, Bim is phosphorylated downstream of growth factor signalling in a MEK-dependent manner, with FGF signalling playing an important role. We suggest that phosphorylation of Bim is a decisive step for the survival of proliferating cells.

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