Cell Signaling: Enzyme-Linked Receptors

Introduction

In the human body, hormones such as insulin and growth hormones interact with cells by enzyme-linked receptors to induce a process inside the cell. An enzyme-linked receptor is a transmembrane protein that responds to signals using an extracellular ligand-binding domain that is linked to a cytoplasmic enzymatic catalytic activity site (Dowd, F. J., & Abel, P. W. (2017). Pharmacodynamics. Pharmacology and Therapeutics for Dentistry, 2–14. https://doi.org/10.1016/b978-0-323-39307-2.00001-1). This means that their active enzyme domain will transform other proteins in the cell once the ligand-binding domain connects to a ligand. The activation of these enzyme-linked receptors will initiate a series of signals that usually will result in gene regulation. Generally, there are four families of enzyme-linked receptors: (1) tyrosine kinase family, (2) guanylate cyclase, (3) tyrosine phosphatase, (4) serine/threonine kinase — all of which have different functions, messengers, and purposes. (Dowd, F. J., & Abel, P. W. (2017b). Pharmacodynamics. Pharmacology and Therapeutics for Dentistry, 2–14. https://doi.org/10.1016/B978-0-323-39307-2.00001-1)

Mechanism

This article in particular will highlight the Receptor Tyrosine Kinase (RTK). As shown in the figure below, the blue strands are receptors. When this RTK binds to the ligands (red circles), two RTKs will come close together to form a cross-linked dimer, which initiates both RTKs’ active enzyme domains. Through a process called ‘cross phosphorylation’, the RTKs will phosphorylate* each others’ tyrosine (the cytoplasmic domain/ the enzyme domain), and these phosphorylated tyrosines create a platform. These platforms are then used to attach and initiate other signal transduction pathways, which are used in gene regulation. (Enzyme Linked Receptors | Nervous system physiology | NCLEX-RN | Khan Academy. (2014, May 4). [Video]. YouTube. https://www.youtube.com/watch?v=kaoRrzakjGE&t=308s)

*Phosphorylation: adding phosphoryl (PO₃) to a molecule, which will transform its shape and therefore activate/deactivate its functions.