Activation Of Protein Kinases By Means Of Stochastic Resonance

2173 words - 9 pages

Short overview
The current technology is based on protein kinase activation by means of stochastic resonance mediated through pulsed electrical fields of very low signal strength. The mode of action reveals how even small pulsed electrical fields can have a major influence on cellular function and physiological consequences.

It is well known that biological sensory systems transform analog quantities such us pressure, temperature, electric fields (E-fields) etc. into trains of information. All the features of systems exhibiting stochastic resonance were found to be present in cell signaling systems which are intrinsically noisy, nonlinear threshold systems. We observed the effects of pulsed electrical fields of intensity near that of the cellular noise and found its effects on a particular protein kinase (Src) turning it into a signaling processing system (Rahbek et al., 2008). The specific phosphorylation level of the Src kinase, essential for its function is controlled by an autophosphorylation step that occurs through processes in which protein subunits exist in different transitional states where phosphorylations can occur in one or some states. We found that interactions between the induced electric field and the charged residues appearing on the proteins can cause a direct transition to their active states by stochastic resonance.
Stochastic resonance is observed when noise added to a system changes the system's behavior in some fashion here by means of pulsed electrical fields. It can occur in bi-stable systems or in systems with a sensory threshold and when the input signal to the system is "sub-threshold". A characteristic feature of stochastic resonance is how signals/noise will cross threshold. For lower noise intensities, the signal does not cause the device to cross threshold, for large noise intensities the output is dominated by the noise leading to a low signal-to-noise ratio. For moderate intensities the noise, however, allows the signal to reach threshold. Thus, a plot of signal-to-noise ratio as a function of noise intensity shows a '∩' shape. We visualize the mechanism as that of a working Brownian ratchet where transitions into a different activated state can be favored. We observed that changing frequencies of E-fields causes enhanced activation from 2 to 100 Hz and that higher frequencies cause reduced activation. Thus the system fulfills the requirements of a stochastic resonance system with a '∩' shaped curve.
Stochastic resonance (SR) occurs in a system with a threshold or barrier such as in a protein when a correct input of information transfer (changes in specific electrical fields effecting charged particles and signal-to-noise ratio) is maximized in the presence of a specific non-zero level of stochastic input noise (such as randomly fluctuating electrical fields) thereby lowering the response threshold. The system will then resonate at a particular noise level. Thus, stochastic resonance is a term...

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