There are many types of interaction domains in signaling proteins. Src homology 2 (SH2) domains and phosphotyrosine-binding (PTB) domains, for example, bind to phosphorylated tyrosines in a particular peptide sequence on activated receptors or intracellular signaling proteins. Src homology 3 (SH3) domains bind to short, proline-rich amino acid sequences. Some pleckstrin homology (PH) domains bind to the charged head groups of specific phosphoinositides that are produced in the plasma membrane in response to an extracellular signal; they
Figure 15–10 Three types of intracellular signaling complexes. (A) A receptor and some of the intracellular signaling proteins it activates in sequence are preassembled into a signaling complex on the inactive receptor by a large scaffold protein.
A signaling complex assembles transiently on a receptor only after the binding of an extracellular signal molecule has activated the receptor; here, the activated receptor phosphorylates itself at multiple sites, which then act as docking sites for intracellular signaling proteins.
Activation of a receptor leads to the increased phosphorylation of specific phospholipids (phosphoinositides) in the adjacent plasma membrane; these then serve as docking sites for specific intracellular signaling proteins, which can now interact with each other.
enable the protein they are part of to dock on the membrane and interact with other similarly recruited signaling proteins (see Figure 15–10C). Some signaling proteins consist solely of two or more interaction domains and function only as adaptors to link two other proteins together in a signaling pathway.
Interaction domains enable signaling proteins to bind to one another in multiple specific combinations. Like Lego® bricks, the proteins can form linear or branching chains or three-dimensional networks, which determine the route followed by the signaling pathway. As an example, Figure 15–11 illustrates how some interaction domains mediate the formation of a large signaling complex around the receptor for the hormone insulin.
Another way of bringing receptors and intracellular signaling proteins together is to concentrate them in a specific region of the cell. An important example is the primary cilium that projects like an antenna from the surface of most vertebrate cells (discussed in Chapter 16). It is usually short and nonmotile and has micro-tubules in its core, and a number of surface receptors and signaling proteins are concentrated there. We shall see later that light and smell receptors are also highly concentrated in specialized cilia.
The Relationship Between Signal and Response Varies in Different Signaling Pathways
The function of an intracellular signaling system is to detect and measure a specific stimulus in one location of a cell and then generate an appropriately timed and measured response at another location. The system accomplishes this task by sending information in the form of molecular “signals” from the sensor to the target, often through a series of intermediaries that do not simply pass the signal along but process it in various ways. All signaling systems do not work in precisely the same way: each has evolved specialized behaviors that produce a response that is appropriate for the cell function that system controls. In the following paragraphs, we list some of these behaviors and describe how they vary in different systems, as a foundation for more detailed discussions later.
1.
Response timing varies dramatically in different signaling systems, according to the speed required for the response. In some cases, such as synaptic signaling (see Figure 15–2C), the response can occur within milliseconds. In other cases, as in the control of cell fate by morphogens during development, a full response can require hours or days.
2.