What Is ERK Phosphorylation?

In cell biology, extracellular signal-regulated kinase (ERK) phosphorylation refers to a signaling pathway comprised of proteins and enzymes involved in cellular processes, namely cell survival and apoptosis. ERK phosphorylation is one of four mitogen-activated protein kinase (MAPK) signaling pathways. The ERK phosphorylation cascade is activated when a tyrosine (Tys) and/or threonine (Thr) kinase receptor molecule activates a protein kinase on the surface of a cell. When the ERK phosphorylation cycle does not function properly, inappropriate ERK activation may occur and abnormal and cancerous cells can develop.

The most basic role of ERK phosphorylation is cell survival; however, there is evidence of a death-promoting role under certain conditions in the cell. Evidence has shown that ERK regulates cell survival and cell death, or apoptosis, at various points along the signaling pathway. The exact mechanism of ERK-induced apoptosis may occur at different levels, both upstream and downstream of the phosphorylation cascade. Scientists have suggested a relationship between ERK’s cell-death role and injury- or stroke-related effects.

Defining ERK phosphorylation requires an explanation of the phosphorylation cascade, which involves a handful of highly specific enzymes and proteins. There are two ERK pathways — kinase-1 (ERK1) and kinase-2 (ERK2), also known as MAPK3 and MAPK1, respectively. ERK activation requires dual phosphorylation by Tys and Thr, starting with Tys phosphorylation. Phosphorylation involves the transfer of one phosphate molecule from an active protein kinase to an inactive protein kinase; an energy-bearing adenosine triphosphate (ATP) molecule donates the phosphate molecule. The activation of one protein kinase results in the phosphorylation of each subsequent protein kinase along the pathway until a protein is activated and a cellular response is elicited.

Cells from different origins require different proteins and/or enzymes to drive the phosphorylation cascade. For every activating protein, there must be a deactivating protein. The activating and deactivating molecules essentially regulate the signal cascade through binding with receptor sites until the appropriate cellular response is complete. Several proteins involved in the ERK phosphorylation cycle have been targeted in cancer treatment therapies because atypical ERK activation has been shown to cause cancer.

In the pharmaceutical industry, therapeutic drugs have been developed to target specific protein receptors, namely, G-coupled protein receptors (GCPRs). G-proteins (Ras, Rac, Rho, Cdc42, etc.) are involved in many physiological processes on a cellular level. Researchers have developed an ERK assay as a tool to measure GCPR activation. An ERK assay such as this enables ERK detection and provides clear and consistent results for drug developers.