Enzyme-Linked Receptors as Drug Targets

Enzyme-Linked Receptors as Drug Target Background

Enzyme-linked receptors are transmembrane receptors, which their ligand-binding domain on the outer surface of the plasma membrane. It's also known as catalytic receptors and includes a great many drug targets such as receptor tyrosine kinases/RTKs, receptors serine/threonine kinasess/RSTKs and receptor tyrosine phosphatases.

Amongst the Enzyme-linked receptors, particular subfamilies may be readily identified dependent on the function of the enzymatic portion of the receptor. The smallest group is the particulate guanylyl cyclases of the natriuretic peptide receptor family.

The most widely recognized group is probably the receptor tyrosine kinase (RTK) family, epitomized by the neurotrophin receptor family, where a crucial initial step is the activation of a signalling cascade by autophosphorylation of the receptor on intracellular tyrosine residue(s) catalyzed by enzyme activity intrinsic to the receptor.

A third group is the extrinsic protein tyrosine kinase receptors, where the catalytic activity resides in a separate protein from the binding site. Examples of this group include the GDNF and ErbB receptor families, where one, catalytically silent, member of the heterodimer is activated upon binding the ligand, causing the second member of the heterodimer, lacking ligand binding capacity, to initiate signaling through tyrosine phosphorylation.

A fourth group, the receptor threonine/serine kinase (RTSK) family, exemplified by TGF-β and BMP receptors, has intrinsic serine/threonine protein kinase activity in the heterodimeric functional unit.

The fifth and final group are the receptor tyrosine phosphatases (RTP), which appear to lack cognate ligands, but may be triggered by events such as cell:cell contact and have identified roles in the skeletal, hematopoietic and immune systems.


1. Alexander S P H, et al. The Concise Guide to PHARMACOLOGY 2015/16: Catalytic receptors[J]. British journal of pharmacology, 2015, 172(24): 5979-6023.

2. Díaz-Díaz G, et al. New materials for analytical biomimetic assays based on affinity and catalytic receptors prepared by molecular imprinting[J]. TrAC Trends in Analytical Chemistry, 2012, 33: 68-80.