Is Phosphorylation a Post-Translational Modification?

Phosphorylation is a widespread and reversible type of post-translational modification. In cellular biology, proteins are the primary molecules that perform a vast array of tasks. They are constructed through a process called translation, where genetic instructions are read and used to assemble chains of amino acids. However, many proteins require additional chemical alterations after their creation to become fully functional.

What Are Post-Translational Modifications?

After a protein is synthesized from messenger RNA, it is often not in its final or active form. Post-translational modifications (PTMs) are chemical changes made to a protein after its initial synthesis. These modifications are a way for cells to expand the functional diversity of their complete set of proteins, known as the proteome.

PTMs can activate or inactivate a protein’s function, guide it to a specific location within the cell, or mark it for degradation when it is no longer needed. They can also change a protein’s stability or how it interacts with other molecules, such as other proteins or DNA. Phosphorylation is just one of many types of PTMs, which also include processes like glycosylation, ubiquitination, and methylation.

Explaining Phosphorylation

Phosphorylation is the biochemical process of adding a phosphate group to a molecule, most often a protein. This reaction is managed by two main families of enzymes. Protein kinases attach phosphate groups to specific sites on proteins, using adenosine triphosphate (ATP) as the phosphate donor, while protein phosphatases remove them in a process called dephosphorylation.

This reversibility allows phosphorylation to act like a molecular switch, turning protein functions on or off in response to cellular signals. The addition of the phosphate group commonly occurs on the side chains of three specific amino acids: serine, threonine, and tyrosine. These amino acids all possess a hydroxyl (-OH) group, which is the site of the phosphate attachment.

Functional Significance of Phosphorylation

The addition of a phosphate group can alter a protein’s properties and function. A phosphate group is both bulky and negatively charged, and introducing it can change a protein’s three-dimensional shape, or conformation. This structural change can directly influence the protein’s activity, for example, by opening or closing the active site of an enzyme, or by altering how it binds to other molecules.

Phosphorylation is a primary component of cell signaling pathways, which transmit information from the outside of a cell to its interior, often culminating in changes to gene expression. These pathways control cell growth, differentiation, and responses to the environment. Phosphorylation also directs the orderly progression of the cell cycle, governs metabolic pathways, and manages programmed cell death, known as apoptosis.

Phosphorylation’s Role in Health and Disease

When the balance between kinase and phosphatase activity is disrupted, it can lead to a wide range of human diseases. This dysregulation can manifest as too much phosphorylation (hyperphosphorylation) or too little (hypophosphorylation). It can also occur at the wrong time or on the wrong protein.

In many cancers, for instance, protein kinases are overactive, driving uncontrolled cell growth. Metabolic disorders like diabetes are linked to problems in phosphorylation-dependent signaling pathways, such as the insulin signaling pathway. Neurodegenerative diseases, including Alzheimer’s disease, are associated with the hyperphosphorylation of the tau protein, which forms tangles in neurons. This has led to therapies, such as kinase inhibitors, that target these pathways.