The receipt of informational signals by a cell is a complex task. For this purpose, cells display an extraordinarily elaborate array of transmembrane proteins termed receptors that function to acquire information from the extracellular space and relay this information into the cell through the plasma membrane . In effect, cell surface receptors act as the antennae of the cell.
Mammalian cells like our own have wide and diverse types of transmembrane receptors, but we will focus only on a subset of them, specifically:
GFs act by binding to cell surface GF receptors. Each type of GF binds to the extracellular domain of its own specific receptor and conversely will not bind to receptors for other growth factors. This extracellular receptor domain can be viewed as having a pocket that specifically accommodates the appropriate growth factor in a lock-and-key fashion and at the same time excludes all others. Thus, epidermal growth factor (EGF) will only bind to the EGF receptor on the surface of cells but not to the PDGF (platelet-derived growth factor) receptor that may also be displayed on the cell surface.
In general, each type of receptor is said to bind specifically to its own ligand . Other ligands besides growth factors may convey signals from cell to cell through intercellular space. There are at least several hundred distinct receptor: ligand pairs in our body, each devoted to the binding of a distinct extracellular ligand such as a growth factor to its cognate receptor. Each ligand originates elsewhere in the tissue or organism, being secreted by a cell or cells specialized for its release.
Recall that kinases are enzymes that attach phosphate groups to their substrates. Protein kinases take the gamma-phosphates from ATP and transfer them to protein substrates, resulting in the phosphorylation of the substrate proteins. In the case of GF receptors, the phosphate groups are attached to the tyrosine side chains of substrate proteins that communicate with or lie near the cytoplasmic domains of the GF receptors. Accordingly, these receptors are considered to have protein tyrosine kinase activity to distinguish them from many other protein kinases throughout the cell that are devoted to other signalling functions and attach phosphates to serine or threonine side chains of their substrates.
The sequence of events is then as follows:
When a GF ligand binds to a single receptor molecule,this encourages the dimerization of the receptor with another one floating nearby in the plasma membrane. Often the GF ligand itself has two receptor-binding ends, enabling it to serve as a bridge between the two receptors that attracts two receptors, encourages their dimerization, and stabilizes the resulting receptor dimer pair. The dimerization of the extracellular domain in turn drags the cytoplasmic domains of the two receptors molecules into close juxtaposition. The tyrosine kinase (TK) of one receptor molecule then phosphorylates the kinase domain of the second receptor molecule with which it has come in close contact following ligand binding. This phosphorylation results in a steric shift in the 3-dimensional structure of the phosphorylated kinase domain and in turn causes its functional activation. In effect, the two kinase domains, once they are brought face-to-face, phosphorylate and thereby activate each other. Once they are activated, they then proceed to phosphorylate a multitude of nearby cytoplasmic substrate proteins that then pass signals further into the cell.