Thrombin‐Cellular Interactions

It is clear that there are a number of different types of reactions between thrombin and the cell surface (TABLE 6). In one type, thrombin binds to cell-surface receptors resulting in cellular activation. In other types of reactions, there are at least two components to the thrombin-specific pathway of cellular activation: a classical receptor to which thrombin binds, and a protein that is cleaved. In both types of reactions, thrombin binding and/or proteolysis is linked to changes in GTP-binding proteins, protein kinase C, or other pathways. In most cases, the receptor and membrane substrates involved in cellular activation are not well characterized. In another type of reaction, the interaction between thrombin and proteins in the extracellular fluid is regulated by cell-surface receptors. Binding of thrombin to these receptors can result in acceleration or inhibition of the reactions with the soluble proteins. In the fourth type of reaction, thrombin cleaves a cell-membrane protein that is involved in reactions with plasma proteins. Recognition of the different types of interactions between thrombin and the cell surface is necessary for the correct interpretation of experimental observations. Although the term receptor has classically referred to a cell-surface component to which an agonist binds, it is now clear that there are additional membrane components that specifically bind potential agonists not leading to cellular activation.