THE DYNAMICS OF RECEPTOR-MEDIATED SIGNALING: ELEGANCE IN CHAOS.
Immunology Group
International Centre for Genetic Engineering and Biotechnology
Aruna Asaf Ali Marg
New Delhi – 110067
The coordinated response of a cell to environmental cues such as growth factors and hormones is mediated through the activation of various signal transduction pathways. Our current perception of signaling pathways is that they constitute a highly complex network that, like most other complex networks, exhibits a scale-free topology. Consequently, the functional outcome of signal transduction would likely represent the integrated result of the intricate and varied interactions between the numerous individual constituents of the network
While overall topology of the signaling network has been revealed, mechanisms that regulate the pathways embedded within this network continue to remain enigmatic. For instance, the question of how the amplitude and rate of signal transfer are modulated is yet unclear. Stimulation of a given cell surface receptor with different agonists is known to evoke diverse cellular responses, although they all activate the same intracellular pathways. This is especially true in the case of lymphocytes, where variations in the nature of antigen receptor triggering can lead to the opposing and extreme outcomes of cell death on the one hand, to proliferation and differentiation on the other. While such observations point to the inherent plasticity of signaling networks, how this is achieved remains to be clarified.
Studies from our laboratory suggest that, during the process of signal transduction, the individual components of the network exhibit chaotic behavior. As a result, transmission of signal through the modules of the network occurs in a non-synchronized manner. Importantly, it is this feature of asynchronic transmission that provides the operational framework for signal processing in a combinatorial manner and thus accounts for the plasticity of the signaling network.