Sensitivity to extracellular signals can vary greatly. Hormones tend to act at very low concentrations on their distant target cells, which are therefore highly sensitive to low concentrations of signal. Neurotransmitters, on the other hand, operate at much higher concentrations at a synapse, reducing the need for high sensitivity in postsynaptic receptors. Sensitivity is often controlled by changes in the number or affinity of the receptors on the target cell. A particularly important mechanism for increasing the sensitivity of a signaling system is signal amplification, whereby a small number of activated cell-surface receptors evoke a large intracellular response either by producing large amounts of a second messenger or by activating many copies of a downstream signaling protein.
3.
Dynamic range of a signaling system is related to its sensitivity. Some systems, like those involved in simple developmental decisions, are responsive
Figure 15–11 A specific signaling complex formed using modular interaction domains. This example is based on the insulin receptor, which is an enzyme-coupled receptor (a receptor tyrosine kinase, discussed later). First, the activated receptor phosphorylates itself on tyrosines, and one of the phosphotyrosines then recruits a docking protein called insulin receptor substrate-1 (IRS1) via a PTB domain of IRS1; the PH domain of IRS1 also binds to specific phosphoinositides on the inner surface of the plasma membrane. Then, the activated receptor phosphorylates IRS1 on tyrosines, and one of these phosphotyrosines binds the SH2 domain of the adaptor protein Grb2. Next, Grb2 uses one of its two SH3 domains to bind to a proline-rich region of a protein called Sos, which relays the signal downstream by acting as a GEF (see Figure 15–8) to activate a monomeric GTPase called Ras (not shown). Sos also binds to phosphoinositides in the plasma membrane via its PH domain. Grb2 uses its other SH3 domain to bind to a proline-rich sequence in a scaffold protein. The scaffold protein binds several other signaling proteins, and the other phosphorylated tyrosines on IRS1 recruit additional signaling proteins that have SH2 domains (not shown).
over a narrow range of extracellular signal concentrations. Other systems, like those controlling vision or the metabolic response to some hormones, are highly responsive over a much broader range of signal strengths. We will see that broad dynamic range is often achieved by adaptation mechanisms that adjust the responsiveness of the system according to the prevailing amount of signal.
4.
Persistence of a response can vary greatly. A transient response of less than a second is appropriate in some synaptic responses, for example, while a prolonged or even permanent response is required in cell fate decisions during development. Numerous mechanisms, including positive feedback, can be used to alter the duration and reversibility of a response.
5.
Signal processing can convert a simple signal into a complex response. In many systems, for example, a gradual increase in an extracellular signal is converted into an abrupt, switchlike response. In other cases, a simple input signal is converted into an oscillatory response, produced by a repeating series of transient intracellular signals. Feedback usually lies at the heart of biochemical switches and oscillators, as we describe later.
6.
Integration allows a response to be governed by multiple inputs. As discussed earlier, for example, specific combinations of extracellular signals are generally required to stimulate complex cell behaviors such as cell survival and proliferation (see Figure 15–4). The cell therefore has to integrate information coming from multiple signals, which often depends on intracellular coincidence detectors; these proteins are equivalent to AND gates in the microprocessor of a computer, in that they are only activated if they receive multiple converging signals (Figure 15–12).
7.