Plasma membrane nanoswitches generate high-fidelity Ras signal transduction

Tian, Tianhai; Harding, Angus; Inder, Kerry L.; Plowman, Sarah J.; Parton, Robert G.; Hancock, John F.

doi:10.1038/ncb1615

Cited by 383 publications

(510 citation statements)

References 44 publications

Supporting

Mentioning

477

Contrasting

Order By: Relevance

“…Galectin-1, by stabilizing H-Ras nanoclusters, leads to enhanced recruitment of effectors and greater signal output. [34] In addition, formation of Ras nanoclusters transforms analog signal input into digital output, [48] which may be related to the potentiation of cellular transformation by Galectin-1. [37,38] Importantly, Ras sublocalization markedly influences which effector pathways are activated and how intensively.…”

Section: Ras: An Actor On Many Stagesmentioning

confidence: 99%

The Ras‐ERK pathway: Understanding site‐specific signaling provides hope of new anti‐tumor therapies

2010

View full text Add to dashboard Cite

Recent discoveries have suggested the concept that intracellular signals are the sum of multiple, site-specified subsignals, rather than single, homogeneous entities. In the context of cancer, searching for compounds that selectively block subsignals essential for tumor progression, but not those regulating ''house-keeping'' functions, could help in producing drugs with reduced side effects compared to compounds that block signaling completely. The Ras-ERK pathway has become a paradigm of how space can differentially shape signaling. Today, we know that Ras proteins are found in different plasma membrane microdomains and endomembranes. At these localizations, Ras is subject to site-specific regulatory mechanisms, distinctively engaging effector pathways and switching-on diverse genetic programs to generate different biological responses. The Ras effector pathway leading to ERKs activation is also under strict, space-related regulatory processes. These findings may open a gate for aiming at the Ras-ERK pathway in a spatially restricted fashion, in our quest for new anti-tumor therapies.

show abstract

Section: Ras: An Actor On Many Stagesmentioning

confidence: 99%

The Ras‐ERK pathway: Understanding site‐specific signaling provides hope of new anti‐tumor therapies

2010

View full text Add to dashboard Cite

show abstract

“…Alternatively, the clustering of Ras could confer beneWcial response properties onto the signaling network. Tian et al explored this possibility by using a mathematical model that coupled nanocluster properties with response properties of cytoplasmic signaling networks to show that the conWnement of Raf molecules to active Ras clusters could lead to high-Wdelity signal transduction (Tian et al 2007). This work thereby represents the Wrst step to bridge the gap between spatial temporal properties of Ras on nanoscales and the phenotypic response on a much larger cellular scale.…”

Section: Signaling Via Protein Clusters In the Plasma Membranementioning

confidence: 99%

Quantitative microscopy and systems biology: seeing the whole picture

Verveer

Bastiaens

2008

Histochem Cell Biol

View full text Add to dashboard Cite

Understanding cellular function requires studying the spatially resolved dynamics of protein networks. From the isolated proteins we can only learn about their individual properties, but by investigating their behavior in their natural environment, the cell, we obtain information about the overall response properties of the network module in which they operate. Fluorescence microscopy methods provide currently the only tools to study the dynamics of molecular processes in living cells with high temporal and spatial resolution. Combined with computational approaches they allow us to obtain insights in the reactiondiVusion processes that determine biological function on the scale of cells.

show abstract

“…Caveolae regulate the nanoscale organization of the plasma membrane to remotely control Ras signaling nanoclustering is inhibited, or nanocluster structure is perturbed Tian et al, 2007;Cho et al, 2012;Zhou et al, 2012;van der Hoeven et al, 2013).…”

Section: Introductionmentioning

confidence: 99%