Receptors with intrinsic enzymatic activity are the second biggest group of receptors after the GPCRs. They include four types according to the form of enzymatic activity of the intracellular domain (Figure 23a).
- Receptor tyrosine kinases (RTKs) On activation, the kinase domain phosphorylates tyrosine amino acid residues. There are seven classes of RTK with different extracellular domains (Figure 23b).
- Receptor serine–threonine kinases On activation, the kinase domain phosphorylates serine and/or threonine amino acid residues.
- Receptor tyrosine phosphatases The intrinsic tyrosine phosphatase activity of the enzymatic domain is suppressed on activation.
- Receptor guanylyl cyclases The enzymatic domain generates the second messenger cGMP from GTP following activation.
Figure 23 (a) The four classes of receptors with intrinsic enzymatic activity. Note that the kinase domains can phosphorylate residues located on the other receptor chain (autophosphorylation) or on other signalling proteins (as shown here). Note that receptors with intrinsic enzymatic activity with the exception of tyrosine phosphatases, have been represented in their active state, that is, following the formation of dimers by the extracellular ligand. In contrast to other receptors, receptor tyrosine phosphatases suppress their enzymatic activity upon ligand binding. (b) The seven subfamilies of receptor tyrosine kinases (RTK). The functional role of most of the cysteine-rich, immunoglubulin-like, and fibronectin-like extracellular domains are not known. Only one member of each subfamily is indicated. Note that the PDGF, FGF and VEGF receptors have a split tyrosine kinase domain; the PDGF receptor is shown in more detail in Figure 25. (EGF = epidermal growth factor; NGF = nerve growth factor; PDGF = platelet-derived growth factor; FGF = fibroblast growth factor; VEGF = vascular endothelial growth factor; Eph = ephrin.)