Pathway Evolution

Cataloging Kinase Targets

Science Signaling  29 Sep 2009:
Vol. 2, Issue 90, pp. ec323
DOI: 10.1126/scisignal.290ec323

Protein phosphorylation is a central mechanism in the control of many biological processes (see the Perspective by Collins). It remains a challenge to determine the complete range of substrates and phosphorylation sites altered by a kinase-like cyclin-dependent kinase 1 (Cdk1), which controls cell division in yeast. Holt et al. engineered a strain of yeast to express a modified Cdk1 molecule that could be inhibited by a specific small-molecule inhibitor. The range of Cdk1-dependent phosphorylation was assessed by quantitative mass spectrometry, which revealed many previously uncharacterized substrates for Cdk1. In addition to phosphorylation on serine and threonine residues, which appears to be evolutionarily ancient, tyrosine phosphorylation occurs primarily in multicellular organisms. Tan et al. compared the overall presence of tyrosine residues in human proteins (which are frequently phosphorylated) and in yeast proteins (which are not). Loss of tyrosine residues has occurred during evolution, presumably to reduce adventitious tyrosine phosphorylation.

C. S. H. Tan, A. Pasculescu, W. A. Lim, T. Pawson, G. D. Bader, R. Linding, Positive selection of tyrosine loss in metazoan evolution. Science 325, 1686–1688 (2009). [Abstract] [Full Text]

L. J. Holt, B. B. Tuch, J. Villén, A. D. Johnson, S. P. Gygi, D. O. Morgan, Global analysis of Cdk1 substrate phosphorylation sites provides insights into evolution. Science 325, 1682–1686 (2009). [Abstract] [Full Text]

M. O. Collins, Evolving cell signals. Science 325, 1635–1636 (2009). [Summary] [Full Text]