2012
DOI: 10.1209/0295-5075/97/58004
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Enhancing phosphorylation cascades by anomalous diffusion

Abstract: A key event in many cellular signaling cascades is the multiple phosphorylation of proteins by specialized kinases. A prototypical example is the mitogen-activated protein kinase (MAPK) that alters the cell's gene transcription after having been phosphorylated twice by the same kinase. Here, we show that anomalous diffusion, induced, for example, by cytoplasmic crowding, can significantly improve the activation of MAPK. Our results on anomalous diffusion with the characteristics of fractional Brownian motion a… Show more

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Cited by 28 publications
(28 citation statements)
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“…Like FBM, OD is also ergodic and stationary (Hofling and Franosch, 2013). Simulations of FBM- and OD-based models agreed favorably with experimentally observed molecular crowding-dependent processive phosphorylation of MAP kinase (Aoki et al, 2011; Hellmann et al, 2012). …”
Section: Theoretical and Physical Constructs Of Anomalous Diffusionsupporting
confidence: 65%
“…Like FBM, OD is also ergodic and stationary (Hofling and Franosch, 2013). Simulations of FBM- and OD-based models agreed favorably with experimentally observed molecular crowding-dependent processive phosphorylation of MAP kinase (Aoki et al, 2011; Hellmann et al, 2012). …”
Section: Theoretical and Physical Constructs Of Anomalous Diffusionsupporting
confidence: 65%
“…As we have seen above, rebindings can qualitatively change the macro scopic behavior of the system in multisite protein modification networks (Abel et al, 2012;Hellmann et al, 2012;Takahashi et al, 2010). Here, a single rebinding event can cause irreversible modification of a species, which then takes the system from one state to another, effectively putting the system onto a different dynamical pathway .…”
Section: How To Model Biochemical Network In the Presence Of Crowdingmentioning
confidence: 97%
“…Crowding can enhance rebindings (Lomholt et al, 2007a,b), which means that crowding can change the response of these multisite protein modification networks (Aoki et al, 2011(Aoki et al, , 2013Hellmann et al, 2012;Takahashi et al, 2010). Recently, this prediction was confirmed experimentally by Aoki et al (2011Aoki et al ( , 2013.…”
Section: Crowding Can Qualitatively Change the Response Of Biochemicamentioning
confidence: 99%
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“…Interestingly, the scaling o f the ensem ble-averaged and tim e-averaged M SD can be different if the underlying random w alk shows a w eak ergodicity breaking [11,12], Recent experim ental data, however, have provided strong evidence that crow ded fluids are viscoelastic on certain scales [13,14] w hich is reflected in a subdiffusive fractional Brow nian m otion o f tracer m acrom olecules on short and interm ediate tim e scales [15][16][17][18], A s a consequence, biochem ical reactions have been predicted to differ strongly from those in purely viscous solutions [19][20][21], In line with this, we recently have been able to show that the opening and closing kinetics o f a single-stranded DNA hairpin not only is slow ed down by crow ding-induced subdiffusion. Rather, also the closed state o f the hairpin was significantly favored in crow ded fluids that feature an anom alous diffusion [22].…”
mentioning
confidence: 99%