Receptor proteins are an integral part of biochemistry and pharmacology. They help in transducing chemical signals across the plasma membrane.
There are different types of receptor proteins. This article will throw light on some of the widely studied receptor proteins in regard to their role in signal transduction.
Receptor protein examples:
- Receptor tyrosine kinase
- Nuclear receptors
- Ligand-gated ion channels
- G protein-coupled receptors
The following sections will discuss the above-mentioned receptor proteins in detail.
Receptor tyrosine kinase
Receptor tyrosine kinases (RTKs) play a crucial role in the progression of different types of cancer.
To date 58 RTKs are identified in humans. RTK receptor proteins regulate normal cellular processes by allowing certain hormones and polypeptide growth hormones to enter the cell. RTKs are of two types: receptor RTKs and non-receptor RTKs. Receptor RTKs consists of a transmembrane domain while non-receptor RTKs are devoid of a transmembrane domain.
Epidermal growth factor receptor and nerve growth factor receptor are the first RTKs to be discovered in1960s. Since then, 20 classes of RTKs have been identified so far.
Some of these are: MuSK RTK, TIE RTK, RTK like orphan receptors, related to receptor tyrosine kinase, leukocyte receptor tyrosine kinase, discoidin domain receptor family, proto-oncogene tyrosine-protein kinase, RET proto-oncogene, epidermal growth factor receptor, tyrosine-protein kinase receptor, insulin receptor.
Eph receptors, platelet-derived growth factor receptors, hepatocyte growth factor receptor, vascular endothelial growth factor, Trk receptors, fibroblast growth factor receptors, and colon carcinoma kinase 4.
Insulin receptor RTK forms dimer linked by disulfide bonds in the presence of insulin. Once a ligand (insulin) binds to the extracellular domain of the receptor, it stimulates dimer formation. A single entity of the dimer has three parts: intracellular C terminal domain, hydrophobic 25 -38 amino acids long transmembrane region, and an extracellular N terminal domain.
The External N terminal region binds the ligand such as a growth factor or insulin. The Internal C terminal region is known to have conserved regions that catalyze the autophosphorylation of RTK substrates.
In the presence of a ligand binding to the extracellular region of the receptor protein, dimers are formed which in turn activates the intracellular C region that catalyzes the autophosphorylation of the activated receptor.
Nuclear receptors are capable of responding to thyroid and steroid hormones. Once activated these receptors regulate the expression of different genes thereby maintaining the homeostasis of the organism.
Nuclear receptors are also known as transcription factors as they directly regulate the expression of certain genes. A nuclear receptor is activated only in the presence of a ligand that upregulates or downregulates the expression of the gene of interest.
Nuclear receptors are different from other receptors in their ability to directly influence gene regulation making them an essential class of receptors to be studied.
The ligands of nuclear receptors are generally lipophilic in nature. Some of these ligands are; Vitamin A and D, xenobiotic hormones, and endogenous hormones.
Mechanisms of nuclear receptors are categorized into two broad classes: type I and type II. Type I nuclear receptors are located in the cytosol and type II nuclear receptors are located in the nucleus. Lipophilic ligands diffusing across the plasma membrane activate these nuclear receptors and stimulate a downstream signaling cascade that ultimately up-regulates or down-regulates gene expression.
Once the type I nuclear receptors get activated in the cytosol, they get translocated to the nucleus and bind to the hormone response elements (specific DNA sequences). Estrogen receptors, progesterone receptors, and androgen receptors are a few examples of type I nuclear receptors.
The DNA/nuclear receptor then transcribes DNA into messenger RNA which in turn leads to protein expression.
Type II nucleus receptors are located in the nucleus. These receptors are bound to corepressor proteins in the absence of ligands. Once the ligands bind to the nuclear receptors, corepressors are replaced by coactivators that activate the receptor. The activated receptor then binds to DNA to transcribe DNA into messenger RNA with the help of other polymerase proteins.
Retinoic acid receptor and thyroid hormone receptor are the two examples of nuclear receptors type II.
There are two other types of mechanisms: type III and type IV.
Like type I nuclear receptors, this class of receptors also binds to DNA as homodimers.
These types of nuclear receptors are capable of binding to DNA as both monomers and dimers.
Ligand-gated ion channels
In the presence of a chemical messenger, ligand-gated ion channels allow the transport of Ca2+, Na+, and K+ ions across the plasma membrane.
Neurotransmitter released upon the excitement of presynaptic neuron binds to receptors.
This leads to a conformational change in the receptor which in turn allows ions to flow across the cell membrane ultimately leading to depolarization or hyperpolarization for excitatory or inhibitor response, respectively.
Ligand-gated ion channels consist of an extracellular ligand-binding domain and a transmembrane region consisting of an ion pore.
Ligand-gated ion channels aid in converting presynaptic chemical signals to postsynaptic electrical signals. There are three families of ligan-gated ion channels: ATP-gated channels, cys-loop receptors, and ionotropic glutamate receptors.
G protein-coupled receptors
G protein-coupled receptors are commonly known as heptahelical receptors as they navigate the cell membrane seven times.
These are evolutionary-related receptor proteins that regulate cellular processes once activated. These receptors get activated either in the presence or absence of ligands. Ligands can bind either transmembrane helices or extracellular N terminals.
Interestingly, G protein-coupled receptors are only present in eukaryotes. The ligands of G protein-coupled receptors vary from small peptides to large proteins. Hormones, neurotransmitters, and pheromones are some of the ligands of G protein-coupled receptors.
Two pathways related to G protein-coupled receptors are the phosphatidylinositol signal pathway and the cAMP signal pathway.
A conformational change in the G protein-coupled receptor could be seen when a ligand binds to it and then it acts as a guanine nucleotide exchange factor (GEF). The activated G protein-coupled receptor then further activates an adjacent G protein by replacing GDP with GTP. GTP bound α subunit of G protein-coupled receptor then dissociates from the original unit and initiates intracellular signaling.
Various roles played by G protein-coupled receptors are involved in metastasis and growth of tumors, regulating mood and behavior, stimulating the sense of smell, maintaining homeostasis, nervous systems both sympathetic and parasympathetic are regulated G protein-coupled receptor, regulating the immune system and cell density.
There are different classes of G protein-coupled receptors viz; fungal mating pheromone receptors, rhodopsin-like, frizzled, metabotropic glutamate, secretin receptor family, and cyclin AMP receptors.
Approximately, 831 human genes code for G protein-coupled receptors.
Altogether it can be concluded that there are different types of receptor proteins that play a pivotal role in regulating cellular processes.