Editors' ChoiceStructural Proteomics

Predicting Kinase Substrates

Science's STKE  21 Jan 2003:
Vol. 2003, Issue 166, pp. tw33-TW33
DOI: 10.1126/stke.2003.166.tw33

The cell uses a vast repository of enzymes called kinases to phosphorylate protein substrates, and the specificity of these kinase-substrate interactions in signaling pathways determines cellular behavior. Identification of new kinase-substrate interactions can reveal new pathway connections and further our understanding of kinase activity in normal and aberrant biological processes. Brinkworth et al. have developed a Web-interfaced program called PREDIKIN http://www.biosci.uq.edu.au/kinsub/home.htm that can predict optimal substrate peptides by using only the amino acid sequence of a given protein kinase as input. The program is based on the analysis of sequence and structural information of several protein kinases. The authors applied PREDIKIN to protein databases to identify already known and new potential substrates for protein serine-threonine kinases involved in two yeast signaling processes: cell cycle control and DNA damage checkpoint. The paper discusses accuracy of the analyses, as well as the caveats in such prediction methodologies.

R. I. Brinkworth, R. A. Breinl, B. Kobe, Structural basis and predication of substrate specificity in protein serine/threonine kinases. Proc. Natl. Acad. Sci. U.S.A 100, 74-79 (2003). [Abstract] [Full Text]