 In this video I will define and provide examples of intracellular receptor proteins and cell surface receptor proteins. During intracellular signaling, a chemical message, the intracellular signal, such as a hormone, is released by the signaling cell and binds to a receptor protein that's either located on the surface of a target cell or within the target cell. If the receptor protein is found within the target cell, that's an intracellular receptor protein, the chemical message that binds to the receptor can be referred to as a ligand, so either a hormone or a neurotransmitter or a growth factor could be referred to as a ligand. The ligand binds to the receptor protein and activates the receptor protein and then the activated receptor protein will then produce an intracellular signal. Lipid soluble hormones are able to diffuse through the plasma membrane, so the lipid soluble hormones will bind to intracellular receptor proteins, forming the receptor hormone complex. Then the receptor hormone complex can function as a transcription factor in the nucleus to stimulate gene transcription and the resulting messenger RNAs can then be translated, forming new proteins that will affect the activity of the cell. An example of a lipid soluble hormone is testosterone or dihydrotestosterone. Testosterone binds to the androgen receptor, which is an intracellular receptor, and then will stimulate the transcription of genes that will have masculinizing effects in the body, for example, stimulating the growth of skeletal muscle to increase the muscle mass in the body. When the intracellular signaling molecule is polar and too large to pass through the plasma membrane, it will have to bind to a cell surface receptor protein, a receptor protein that's embedded in the plasma membrane. The signaling molecule is also known as a ligand, and the ligand will bind to a binding site on the receptor, causing a change in the shape of the receptor that can then stimulate the production of an intracellular signal. One type of cell surface receptor protein is an ion channel linked receptor, which is also known as a ligand-gated ion channel. We'll see an example of this where the neurotransmitter is the intracellular signaling molecule that is the ligand binding to the cell surface receptor, and when the ligand-gated ion channel or ion channel linked receptor becomes activated, it changes shape in order to open the ion channel, allowing ions to flow into the cell can then create an intracellular signal. The nicotinic acetylcholine receptor is an example of an ion channel linked receptor or ligand-gated ion channel. Acetylcholine is a neurotransmitter that is released by motor neurons. Acetylcholine is a water-soluble neurotransmitter and will bind to a cell surface receptor. The nicotinic acetylcholine receptor will function as an ion channel linked receptor. When acetylcholine binds to the nicotinic acetylcholine receptor, the receptor will open an ion channel that allows sodium ions to enter the cell. And then as sodium ions flow into the cell, this will excite an electrical impulse known as an action potential. The action potential then spreads through muscle fibers and will stimulate the contraction mechanism. Another class of cell surface receptor proteins are G-protein linked receptors. The beta-adrenergic receptor is an example of a G-protein coupled receptor when the water-soluble hormone epinephrine binds to a binding site of the extracellular domain of the beta-adrenergic receptor. The beta-adrenergic receptor will become activated, it will change its shape, and this will lead to the activation of a G-protein. Then the G-protein will dissociate from the receptor and can then bind to an enzyme. The enzyme adenylyl cyclase will be activated by the G-protein and adenylyl cyclase catalyzes the conversion of ATP, adenosine triphosphate, into cyclic AMP, cyclic adenosine monophosphate. Cyclic AMP is the second messenger in this pathway that will then bind to proteins including protein kinase A. Protein kinase A will be activated by cyclic AMP and protein kinase A can then catalyze phosphorylation of other proteins in order to regulate their activity. We'll see in the phosphorylation cascade that is activated by the beta-adrenergic receptor to stimulate glycogenolysis that protein kinase A will phosphorylate another kinase known as glycogen phosphorylase kinase, then glycogen phosphorylase kinase will phosphorylate glycogen phosphorylase the enzyme that will catalyze hydrolysis of the polysaccharide glycogen to release glucose monomers. G-protein linked receptors are cell surface receptors that are integral membrane proteins that have an extracellular domain that contains the binding site for the ligand which is the intercellular signal such as the water soluble hormone epinephrine. And they also have an intracellular domain that binds to the G-protein so a G-protein linked receptor has seven transmembrane domains that cross the plasma membrane and this connects the extracellular domain with the intracellular domain. When the ligand binds to the extracellular domain it will cause a change in the shape of the intracellular domain leading to activation of the G-protein. The G-protein is called a G-protein because it's bound to either a guanosine triphosphate GTP or a guanosine diphosphate GDP. When the ligand binds to the G-protein linked receptor activating the G-protein the G-protein will dissociate from the receptor and will release a bound GDP. The G-protein of a G-protein linked receptor is known as a heterotrimeric G-protein because it contains three subunits, an alpha subunit, a beta subunit, and a gamma subunit. The alpha subunit contains the binding site for GDP or GTP. When the G-protein becomes activated it will release GDP and exchange it for GTP. Then the activated G-protein can stimulate an intracellular signal to regulate a cellular response such as activating the enzyme adeno-wheel cyclase. Then the GTP in the alpha subunit will be broken down by hydrolysis to form GDP in inorganic phosphate. This will inactivate the G-protein, the alpha, beta, and gamma subunits will then join back together with the receptor and the receptor can now be activated again when the ligand binds to the extracellular domain. Enzyme linked receptors are another category of cell surface receptor proteins. When the ligand binds to the receptor the receptor will become activated as an enzyme that can catalyze a chemical reaction. The receptor tyrosine kinases are a large subgroup of enzyme linked receptors and the epidermal growth factor receptor EGFR is a specific example of a receptor tyrosine kinase. When the ligand epidermal growth factor binds to the epidermal growth factor receptor the epidermal growth factor receptor will become activated and then two epidermal growth factor receptors that have both been activated will join together to form a dimer then the catalytic unit of the epidermal growth factor receptor will catalyze phosphorylation of tyrosine residues amino acids that are on the intracellular region of the adjacent receptor. These phosphorylated tyrosine residues then will bind to other signaling proteins inside the cell to stimulate an intracellular signal. In the case of the epidermal growth factor receptor we'll see that scaffolding proteins bind to the phosphorylated EGFR and then stimulate a RasG protein. The RasG protein then will activate the extracellular signal regulated kinase phosphorylation cascade the ERC phosphorylation cascade eventually leading to mitotic cell division to stimulate tissue growth.