Phosphorylation cascade

A phosphorylation cascade is a sequence of signaling pathway events where one enzyme phosphorylates another, causing a chain reaction leading to the phosphorylation of thousands of proteins. This can be seen in signal transduction of hormone messages. A signaling pathway begins at the cell surface where a hormone or protein binds to a receptor at the extracellular matrix. The interactions between the molecule and receptor cause a conformational change at the receptor, which activates multiple enzymes or proteins. These enzymes activate secondary messengers, which leads to the phosphorylation of thousands of proteins. The end product of a phosphorylation cascade is the changes occurring inside the cell. These cascades work to amplify the signal where binding of one extracellular ligand can activate thousands of proteins downstream since these are allosterically regulated enzymes that make many products, amplifying the signal.

MAP/ERK Phosphorylation Cascade

An example of a signaling pathway that uses phosphorylation cascades is with the activation of mitogen-activated protein (MAP) kinase or ERK kinase. To activate this kinase, an epidermal growth factor must bind to the epidermal growth factor receptor at the extracellular domain, causing a conformational change to the receptor tyrosine kinase that activates it and results in dimerization and autophosphorylation of intracellular tyrosine residues. This allows for the binding of the adaptor protein GRB2 with its SH2 domain, which recognizes the phosphorylated tyrosines.