 In this video, I will describe the role of signal transduction pathways in responding to extracellular signals, define second messenger and provide examples, define phosphorylation cascade and provide examples, describe the cell surface receptor proteins, signal transduction pathways, and corresponding cellular responses for the specific examples of stimulation of glycogenolysis by epinephrine and stimulation of cell proliferation by epidermal growth factor. A signal transduction pathway is a type of intracellular signal, which is a cascade of biochemical events occurring within a cell in order to regulate a cellular response following the activation of a receptor protein, which is usually a cell surface receptor. A intracellular receptor protein binds a lipid soluble hormone forming the receptor hormone complex that can function directly as the intracellular signal and does not require a signal transduction pathway. In contrast, cell surface receptors such as the G protein linked receptors will lead to a signal transduction pathway where there is a cascade of biochemical events with one protein activating another protein. Here we see the receptor activates the G protein and the G protein then activates the enzyme adeno-wheel cyclase. Often a signal transduction pathway will involve a second messenger. A second messenger is a small chemical that functions as an intracellular signal. Typically second messengers are not proteins. An example of a second messenger that we see here is cyclic AMP. Adeno-wheel cyclase is the enzyme that produces the second messenger cyclic AMP from ATP. Here we see the chemical reaction that's catalyzed by the enzyme adeno-wheel cyclase. Adenosine triphosphate ATP is converted to cyclic adenosine monophosphate cyclic AMP as two phosphate groups are released forming another product known as pyrophosphate. One of the phospholipids that forms the plasma membrane known as PIP2 or phosphatidylinositol diphosphate can be converted to two second messenger molecules known as DAG which stands for diaceoglycerol and IP3 which stands for inositol triphosphate. The enzyme phospholipase C catalyzes the conversion of PIP2 into DAG and IP3. Glycogen is a polysaccharide produced in animal cells that is composed of repeating glucose monomers. Glycogen synthesis or glycogenesis is a dehydration synthesis reaction catalyzed by glycogen synthase. Glycogenolysis is hydrolysis of glycogen to release glucose. The enzyme glycogen phosphorylase catalyzes the hydrolysis of glycogen to produce glucose in the mechanism of glycogenolysis. Epinephrine which is also known as adrenaline is a water soluble hormone secreted by the adrenal gland in response to stress. One of the effects of epinephrine is to stimulate glycogenolysis. This will release glucose into the blood from the liver and glucose then will be broken down by cells throughout the body to provide energy that will help those cells cope with stress. Epinephrine will bind to the beta-adrenergic receptor, a G-protein linked receptor that's a cell surface receptor on the surface of cells in the liver. When the beta-adrenergic receptor is activated by epinephrine it will change shape activating the heterotrimeric G-protein and the G-protein will then stimulate the enzyme adenylyl cyclase to produce the second messenger cyclic AMP. Then cyclic AMP will activate a phosphorylation cascade. A phosphorylation cascade is a sequence of multiple protein kinases that phosphorylate other proteins to regulate a cellular response. So a kinase is an enzyme that performs phosphorylation adding a phosphate group to a molecule in contrast a phosphatase is an enzyme that removes the phosphate group from a molecule. In this phosphorylation cascade we'll see that phosphorylation will activate the target protein that becomes phosphorylated although in some cases phosphorylation can inactivate or turn off a protein. Cyclic AMP binds to protein kinase A and activates this enzyme. We commonly abbreviate protein kinase A, PKA. Once activated by cyclic AMP, PKA will phosphorylate GPK. GPK stands for glycogen phosphorylase kinase. Once activated by phosphorylation, glycogen phosphorylase kinase or GPK will go on to phosphorylate another enzyme known as glycogen phosphorylase or GP. Glycogen phosphorylase is the enzyme that catalyzes hydrolysis of glycogen in the mechanism of glycogenolysis. Now let's look at the example of the intracellular signal transduction pathway stimulated by epidermal growth factor. Epidermal growth factor binds to a cell surface receptor that is an enzyme-linked receptor protein known as the EGFR, epidermal growth factor receptor. The EGFR is a receptor tyrosine kinase that will phosphorylate another EGFR. So two EGFR proteins will form a dimer that phosphorylate one another completing the activation of EGFR. Then the active EGFR will stimulate the small G protein RAS, R-A-S. Once activated, RAS will in turn activate a kinase known as RAAF. And RAAF is the first kinase in the ERC phosphorylation cascade. So RAAF will phosphorylate MEK, activating it, and MEK will phosphorylate ERC, activating it. Then ERC will go on to phosphorylate a variety of other proteins ultimately leading to increased transcription of cyclin genes and increased translation of the resulting messenger RNA to produce cyclin proteins that will accelerate the cell cycle, stimulating cell proliferation, or mitotic cell division.