Many signalling proteins have both a catalytic domain and sometimes several binding domains. Some only have binding domains, enabling their proteins to act as adaptor, scaffold or anchoring proteins to bring other proteins together. Because of this multiplicity of binding domains, signalling proteins can potentially combine to form complexes with many other proteins; these complexes may be either transient (e.g. in response to stimulation by a growth factor), or stable (to target a protein to an appropriate location).
However, protein–protein interactions are not random, as the specific interactions between binding domains and their recognition sites will determine the precise route(s) that a signal transduction pathway will take.
Figure 12 shows a hypothetical signalling cascade, drawn to illustrate how different protein domains have specific functions that result in an ordered network of consecutive protein–protein interactions – in other words, in a signal transduction pathway. Receptor activation by an extracellular signalling molecule leads to the phosphorylation of tyrosine residues on the receptor and of inositol phospholipids on the cytosolic face of the plasma membrane , thereby creating temporary docking sites for an array of SH2- and PH-containing signalling proteins.
A cytosolic signalling protein (shown as signalling protein X) contains three different binding domains plus a catalytic kinase domain. On stimulation by an extracellular signalling molecule, signalling protein X translocates to the plasma membrane by virtue of interactions between its SH2 domain and a phosphorylated tyrosine on the receptor protein (sometimes referred as phosphotyrosine or pY), and between its PH domain and phosphorylated inositol phospholipids in the cytosolic leaflet of the lipid bilayer.
This translocation results in a change of conformation in protein X, which unfolds a PTB domain, allowing it to bind a phosphorylated tyrosine in protein Y. The kinase domain in signalling protein X then phosphorylates signalling protein Y on another tyrosine, which subsequently binds to the SH2 domain of an adaptor protein. The SH3 domain in the adaptor protein binds to a proline-rich motif on signalling protein Z. This interaction brings protein Z close to protein Y, such that protein Z is phosphorylated at a tyrosine residue. The signal is then relayed downstream by the activated protein Z.
Figure 13 shows the diversity and flexibility of protein-binding domains in some examples of signalling proteins (discussed later in this chapter).