Protein tyrosine phosphorylation is a fundamental mechanism for controlling many aspects of cellular processes, as well as aspects of human health and diseases. Compared with phosphoserine and phosphothreonine, phosphotyrosine signaling is more tightly regulated, but often more challenging to characterize, due to significantly lower levels of tyrosine phosphorylation (1). While phosphorylation in general is fairly common, tyrosine phosphorylation is very rare.
Extracellular Signal-Regulated Kinases (ERK) also known as the Mitogen-activated Protein Kinase (MAPK), MAPK/ERK proteins are a family of protein-serine/threonine kinases that are activated via the phosphorylation of tyrosine. MAPK/ERK are activated by diverse mechanisms.
Over the past two decades, it has become clear that tyrosine phosphorylation plays a pivotal role in a variety of important signaling pathways in multicellular organisms. In the typical vertebrate cell, phosphotyrosine represents only a tiny fraction of total protein phosphorylation. Yet it is sufficient enough to induce malignant transformation (1), as unregulated phosphotyrosine signaling causes a breakdown in the normal regulation of cellular processes leading to several human diseases (2).
Phosphotyrosine is the phosphorylated version of the amino acid tyrosine, which results from the activation of intracellular protein kinases (e.g. via growth factors) during normal growth and development, well as in transformation and oncogenesis. Phosphorylation of histidine, serine, threonine and tyrosine residues acts as a signaling system to control many cellular signaling pathways.
