Molecular Biology of the Cell by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter by by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morg

PRINCIPLES OF CELL SIGNALING
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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. Coordination of multiple responses in one cell can be achieved by a single
extracellular signal. Some extracellular signal molecules, for example, stimulate
a cell to both grow and divide. This coordination generally depends
on mechanisms for distributing a signal to multiple effectors, by creating
branches in the signaling pathway. In some cases, the branching of signaling
pathways can allow one signal to modulate the strength of a response to
other signals.
Given the complexity that arises from behaviors like signal integration, distribution,
and feedback, it is clear that signaling systems rarely depend on a simple
linear sequence of steps but are often more like a network, in which information
flows not just forward but in multiple directions—and sometimes even backward.
A major research challenge is to understand the nature of these networks and the
response behaviors they can achieve.
A
plasma
membrane
B
The Speed of a Response Depends on the Turnover of Signaling
Molecules
The speed of any signaling response depends on the nature of the intracellular
signaling molecules that carry out the target cell’s response. When the response
requires only changes in proteins already present in the cell, it can occur very rapidly:
an allosteric change in a neurotransmitter-gated ion channel (discussed in
Chapter 11), for example, can alter the plasma membrane electrical potential in
milliseconds, and responses that depend solely on protein phosphorylation can
occur within seconds. When the response involves changes in gene expression
and the synthesis of new proteins, however, it usually requires many minutes or
hours, regardless of the mode of signal delivery (Figure 15–13).
It is natural to think of intracellular signaling systems in terms of the changes
produced when an extracellular signal is delivered. But it is just as important to
consider what happens when the signal is withdrawn. During development, transient
extracellular signals often produce lasting effects: they can trigger a change
in the cell’s development that persists indefinitely through cell memory mechanisms,
as we discuss later (and in Chapters 7 and 22). In most cases in adult tissues,
however, the response fades when a signal ceases. Often the effect is transient
ATP
ADP
P
Y
DOWNSTREAM SIGNALS
ATP
ADP
Figure 15–12 Signal integration.
Extracellular signals A and B activate
different intracellular signaling pathways,
each of which leads to the phosphorylation
of protein Y but at different sites on the
protein. Protein Y is activated only when
both of these sites are phosphorylated,
and therefore MBoC6 it m15.20/15.12
becomes active only when
signals A and B are simultaneously present.
Such proteins are often called coincidence
detectors.
P