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The regulation of protein phosphorylation

DOI: 10.1042/BST0370627 DOI Help
PMID: 19614568 PMID Help

Authors: Louise Johnson (Diamond Light Source)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Biochem Soc Trans , VOL 37 , PAGES 627-641

State: Published (Approved)
Published: August 2009

Abstract: Phosphorylation plays essential roles in nearly every aspect of cell life. Protein kinases regulate signalling pathways and cellular processes that mediate metabolism, transcription, cell-cycle progression, differentiation, cytoskeleton arrangement and cell movement, apoptosis, intercellular communication, and neuronal and immunological functions. Protein kinases share a conserved catalytic domain, which catalyses the transfer of the ?-phosphate of ATP to a serine, threonine or tyrosine residue in protein substrates. The kinase can exist in an active or inactive state regulated by a variety of mechanisms in different kinases that include control by phosphorylation, regulation by additional domains that may target other molecules, binding and regulation by additional subunits, and control by protein–protein association. This Novartis Medal Lecture was delivered at a meeting on protein evolution celebrating the 200th anniversary of Charles Darwin's birth. I begin with a summary of current observations from protein sequences of kinase phylogeny. I then review the structural consequences of protein phosphorylation using our work on glycogen phosphorylase to illustrate one of the more dramatic consequences of phosphorylation. Regulation of protein phosphorylation is frequently disrupted in the diseased state, and protein kinases have become high-profile targets for drug development. Finally, I consider recent advances on protein kinases as drug targets and describe some of our recent work with CDK9 (cyclin-dependent kinase 9)–cyclin T, a regulator of transcription.

Journal Keywords: Phosphosphorylation; Protein Kinases; Protein Structure; Protein Function

Subject Areas: Biology and Bio-materials, Medicine


Technical Areas: