Phosphoserine

By Jamshed Arslan Pharm.D., PhD.

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.

Phosphoserine, the phosphorylated modification of the amino acid serine, is a central post-translational modification within a cell for many biological and biomedical processes. The phosphorylation of specifically four residue types - histidine, serine, threonine, and tyrosine occurs both within the cell as well as at the cell surface. This exquisitely controlled regulatory system controls a vast number of intertwined and interconnected downstream signaling pathways and cascades.

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).

Phosphoserine is an ester of serine and phosphoric acid which results from posttranslational modifications. Phosphorylation is a key post-translational modification necessary for normal cellular signaling.

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.