A number of hormone and growth factor receptors are distinctive in that they contain an intrinsic enzymatic activity and a single membrane-spanning domain. An example of this this class of receptors is the insulin receptor, for which no second messengers have yet been detected.

The insulin receptor (Figure 23.15) is a glycoprotein with an 22 tetrameric structure, stabilized by disulfide bonds. Both the chain (735 residues) and the chain (620 residues) are translated from a single mRNA, giving a polypeptide chain that then undergoes proteolytic processing. The chain, which is thought not to span the membrane, is believed to bind insulin near its C-terminus. The chain has a transmembrane domain, with its C-terminus in the cell interior. The C-terminal region of the chain is the site of a protein tyrosine kinase activity, which is stimulated by the binding of insulin to the extracellular part of the receptor.

The kinase activity is essential to the biological activity of the insulin receptor, because some cases of non-insulin-dependent diabetes are associated with receptor mutations that abolish the kinase activity.

Given that insulin can be considered a growth factor, it is of interest that protein tyrosine kinase activity is found in other growth factor receptors, too, including the following

1. Epidermal growth factor (EGF);

2. Platelet-derived growth factor (PDGF) (Figure 23.24);

3. Colony-stimulating factor 1 (CSF-1);

4. Fibroblast growth factor (FGF); and

5. Insulin-like growth factor 1 (IGF-1).

These receptors are a family of closely related proteins (see Figure 23.15), sharing amino acid sequence homology in the domains with tyrosine kinase activity. There is evidence that the action of insulin as a growth factor is mediated through its binding to one of these receptors, the IGF-1 receptor.

Other, more distantly related membrane receptors have other enzyme activities, such as the following:

1. Proteins of the transforming growth factor (TGF-) bind to a receptor that has a protein serine/threonine kinase activity (like cAMP-dependent protein kinase).

2. Atrial natriuretic factor, which controls blood volume, binds to a receptor that has both a guanylate cyclase activity and a predicted protein serine/threonine kinase activity.