protein phosphorylation

Protein phosphorylation affects most, if not all, cellular activities in eukaryotes and is essential for cell proliferation and development. An estimated 30% of cellular proteins are phosphorylated, representing the phosphoproteome, and phosphorylation can alter a protein’s function, activity, localization and stability.

Specificity

Phosphorylation events are key to most nuclear and cytoplasmic processes. Cellular protein kinases and phosphatases are involved in the regulation of differentiation, cell division, transcription, and DNA repair. Phosphorylation and dephosphorylation can either activate or inactivate other proteins.

A typical protein kinase must recognize between one and a few hundred bona fide phosphorylation sites in a background of approximately 700,000 potentially phosphorylatable residues. Multiple mechanisms have evolved that contribute to this exquisite specificity, including the structure of the catalytic site, local and distal interactions between the kinase and substrate, the formation of complexes with scaffolding and adaptor proteins that spatially regulate the kinase, systems-level competition between substrates, and error-correction mechanisms. The responsibility for the recognition of substrates by protein kinases appears to be distributed among a large number of independent, imperfect specificity mechanisms.

See also

 Kinases

• tyrosine kinases
• serine/threonine kinases (STKs)

References

 Ubersax JA, Ferrell JE Jr. Mechanisms of specificity in protein phosphorylation. Nat Rev Mol Cell Biol. 2007 Jul;8(7):530-41. PMID: 17585314

 Ptacek J, Snyder M. Charging it up: global analysis of protein phosphorylation. Trends Genet. 2006 Oct;22(10):545-54. PMID: 16908088

 Rothman DM, Shults MD, Imperiali B. Chemical approaches for investigating phosphorylation in signal transduction networks. Trends Cell Biol. 2005 Sep;15(9):502-10. PMID: 16084095