Tyrosine Kinase Receptor

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Tyrosine Kinase Receptor

tyrosine-kinase-receptorIn addition to phagocytosis and pinocytosis, there is a whole category of endocytosis called receptor-mediated. Among these receptors, there are those that require the cell to expend energy and those that do not (active transport vs passive transport). Enzyme-linked receptors perform endocytosis as active transport, and most of these are receptor tyrosine kinase (RTK).

Biochemistry Terms, Enzymes and Enzyme-linked Receptors

Recall from chemistry that a chemical compound can be of two main types: structures that are held together by covalent chemical bonds and those held together by ionic bonds. The resulting chemical product of a covalent bond is called a molecule and the result of an ionic bond is often just called a compound or by the practical name of the product (like NaCl is called salt). An organic compound is a chemical compound whose chemical formula contains carbon. Some organic compounds formed by ionic bonds include amino acids and neurotransmitters. A biomolecule is any molecule that is present in living organisms and serves as an important part of biological processes; some examples are proteins, carbohydrates, lipids, antigens, hormones, and nucleic acids.
A protein is a large biomolecule (often called macromolecules in biochemistry) that forms from covalent bonds between one or more long chains of amino acid residues – atoms or groups of atoms left over from a process or chemical reaction. Enzymes are proteins (and in rare cases, nucleic acids) that act as catalysts for chemical reactions, meaning that they cause and / or speed up reactions but aren’t part of the chemical structure of the reactants or products. The structure that the enzyme most directly acts upon is called the substrate and the substrate reacts with the reagent to produce the product(s). Enzyme-linked receptors bind with a special substance called a ligand, triggering an enzymatic reaction with a substrate and its reagent that results in the product, and this enzymatic activity is responsible for many cellular functions, depending upon the type of receptor, ligand, substrate, and other factors.

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Receptors Tyrosine Kinase and RTK-mediated Endocytosis

Tyrosine is an amino acid (one of 22 types) necessary for cellular protein synthesis. A kinase is an enzyme that phosphorylates its substrate – it catalyzes a reaction between its substrate and an energy-carrier molecule like ATP, resulting in the ATP losing a phosphate group to react with the substrate to form a product that is highly energized. Receptors tyrosine kinase are transmembrane proteins that are integrated into the cell membrane, reacting to ligands on the extracellular side and substrates on the intracellular side. The base structure is a protein that hosts tyrosines on the intracellular side and a receptor on the extracellular side. Once fully activated, RTKs trigger many important cellular functions such as growth, cell differentiation, mitotic cycles (reproduction), endocytosis, and even negative effects like the creation of cancer cells.

Prior to binding with a ligand on the extracellular side, an RTK exists as a monomer of tyrosines with a receptor. Upon ligand binding, two monomers come together to form a dimer, and the RTK is then considered activated. This dimer then takes, on the intracellular side, phosphate groups from ATP molecules and has them react with a substrate, resulting in an energized product that triggers a cellular response and performs an important function. Among the most important of these is endocytosis.

For endocytosis in a eukaryotic cell, receptors tyrosine kinase catalyze a reaction between the substrate dynamin and the phosphate groups taken from ATP molecules. Dynamin is a GTPase, which is a special type of enzyme that catalyzes hydrolysis – the breaking up of chemical bonds by the addition of water. Dynamin’s reaction with the energized phosphate groups results in a product that induces scission in the cell membrane, the budding off of a vesicle that transports the substance(s) entering the cell. This product also works with a special protein called clathrin and adaptor proteins to create a clathrin-coated vesicle. Where on the plasma membrane clathrin is not present, RTKs often trigger endocytosis as a part of a flexible combination of lipids in the cell membrane dubbed a lipid raft. Once the entering substance(s) are transported into the cell, to where they are needed, since RTKs were part of the transport vesicle, they can themselves be degraded within the cell or recycled back into the cell membrane.

Summary

Just as exocytosis can be signal-induced, endocytosis can be triggered by a signal pathway created by the binding of certain extracellular and intracellular substances with transmembrane proteins called receptors. One type of receptor, found only in eukaryotes, is called the G protein coupled receptor, a transmembrane protein of seven connected helices that are permanently integrated with the cell membrane. With a specific type of ligand bound to its extracellular side and a typically pre-coupled G protein bound at its intracellular side, the GPCR creates a signal pathway into the cell that triggers activity, such as endocytosis. The GPCR, however, is by no means limited to this activity; in fact, it has a role in just about every basic body function and faculty in the advanced life form cells it is present in.

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