Signaling Cascades Modulate the Speed of Signal Propagation through Space

نویسندگان

  • Christopher C. Govern
  • Arup K. Chakraborty
چکیده

BACKGROUND Cells are not mixed bags of signaling molecules. As a consequence, signals must travel from their origin to distal locations. Much is understood about the purely diffusive propagation of signals through space. Many signals, however, propagate via signaling cascades. Here, we show that, depending on their kinetics, cascades speed up or slow down the propagation of signals through space, relative to pure diffusion. METHODOLOGY/PRINCIPAL FINDINGS We modeled simple cascades operating under different limits of Michaelis-Menten kinetics using deterministic reaction-diffusion equations. Cascades operating far from enzyme saturation speed up signal propagation; the second mobile species moves more quickly than the first through space, on average. The enhanced speed is due to more efficient serial activation of a downstream signaling module (by the signaling molecule immediately upstream in the cascade) at points distal from the signaling origin, compared to locations closer to the source. Conversely, cascades operating under saturated kinetics, which exhibit zero-order ultrasensitivity, can slow down signals, ultimately localizing them to regions around the origin. CONCLUSIONS/SIGNIFICANCE Signal speed modulation may be a fundamental function of cascades, affecting the ability of signals to penetrate within a cell, to cross-react with other signals, and to activate distant targets. In particular, enhanced speeds provide a way to increase signal penetration into a cell without needing to flood the cell with large numbers of active signaling molecules; conversely, diminished speeds in zero-order ultrasensitive cascades facilitate strong, but localized, signaling.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Positional Information Generated by Spatially Distributed Signaling Cascades

The temporal and stationary behavior of protein modification cascades has been extensively studied, yet little is known about the spatial aspects of signal propagation. We have previously shown that the spatial separation of opposing enzymes, such as a kinase and a phosphatase, creates signaling activity gradients. Here we show under what conditions signals stall in the space or robustly propag...

متن کامل

The Jak-Stat Signaling Pathway of Interferons System: Snapshots

Interferons (IFNs) are a family of small regulatory glycoproteins that play a central role in the defense against viral infections. Although IFNs have been initially discovered as antiviral factors, today they are known as an integral part of the cytokine network that affect a wide range of biological processes. IFNs exert their pleiotropic effects through their multisubunit cell surface recept...

متن کامل

Reactive Oxygen Species Link Gonadotropin-Releasing Hormone Receptor Signaling Cascades in the Gonadotrope

Biological rhythms lie at the center of regulatory schemes that control many aspects of living systems. At the cellular level, meaningful responses to external stimuli depend on propagation and quenching of a signal to maintain vigilance for subsequent stimulation or changes that serve to shape and modulate the response. The hypothalamus-pituitary-gonad endocrine axis that controls reproductive...

متن کامل

The Expression of Signal Regulatory Protein-alpha in Normal and Osteoarthritic Human Articular Cartilage and Its Involvement in Chondrocyte Mechano-transduction Response

Signal regulatory proteins (SIRP) belong to immunoglobulin super family (IgSF) and relate to integrin signaling cascades. It has been shown that SIRPa is expressed in a variety of cells including myeloid cells and neurons. In the present study the expression of this IgSF member in articular chondrocytes was investigated. Methods: Using a panel of anti-SIRPalpha antibodies, immunohistochemistry...

متن کامل

Plume outflow intrusion impact on acoustical signal fluctuations in a pre-stratified environment

Existence of outflow intrusion introduces small-scale turbulence that perturbs the vertically stratified character of the sound velocity and causes spatial and temporal fluctuations of the sound propagation. In this experimental study, we have investigated acoustic wave propagation with frequency of 50 kHz in a pre-stratified environment with intrusion of a turbulent plume while the si...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • PLoS ONE

دوره 4  شماره 

صفحات  -

تاریخ انتشار 2009