Signaling Pathways

Enzyme-Coupled Surface Receptors

Receptor tyrosine kinases (RTKs) are a large and diverse group of enzyme-coupled receptors that activate many kinds of cellular events, including cellular growth and differentiation.

Protein function can be altered by an enzyme called protein kinase, which phosphorylates proteins to activate them. A special class of cellular receptors uses protein kinase to trigger a cellular response. While there are many different types of kinases, the primary receptor acts on tyrosine. A receptor tyrosine kinase (RTK) is a membrane receptor kinase that phosphorylates (adds a phosphate group to) the amino acid tyrosine of a substrate protein. Its action can lead to many different cellular responses, and nearly every aspect of the cell is influenced by these receptors. Cell metabolism, growth, development, division, and movement are all affected by RTK receptors. RTKs bind to the ligands of different types of growth factors, such as epidermal growth factor and platelet-derived growth factor, to activate ten or more different pathways and cellular responses. Multiple signals can be generated at once, allowing the cell to perform and regulate many tasks at the same time.

Before the signaling molecule binds with the RTK receptor, the receptor is a single unit that spans the membrane from the extracellular space to the cytoplasm. Once a ligand binds two individual receptors, they form a dimer. A dimer is the union of two receptor tyrosine kinase molecules, which forms in response to receiving a signal. Once the dimer is formed, each RTK protein adds phosphate groups on the cytoplasm side of its partner, activating both proteins. Relay proteins inside the cell recognize the phospho-tyrosine molecules and bind to them, changing their structures. The RTK proteins and the relay proteins can then activate and initiate the appropriate cellular response.

An example of an RTK is the epidermal growth factor (EGF) receptor. When EGF binds to the receptor, it encourages rapid cell division and replication by amplifying the signal that drives the cell cycle through various checkpoints. EGF works as a transcription factor during the activation of gene expression modules as proteins are being synthesized. Under normal conditions in a human adult, growth factors are tightly controlled to prevent overgrowth of cells, which can become cancer. There are negative feedback events that occur that limit the length of time the cell remains in different stages and how active the RTKs are in the process. When the EGF receptor is activated, it automatically signals the negative feedback loop that will shut it down when the processes get to a specific point. Using negative feedback in this manner has shown to preserve the stability of the cell processes in the case of changes to the cell's environmental conditions or additional stresses added to the system.

Receptor Tyrosine Kinase

Receptor tyrosine kinases (RTKs) are membrane receptors that form dimers (pairs) when ligands bind to them. They activate each other by adding phosphates to their intracellular kinase ends, which then phosphorylate other proteins, triggering a cellular response.