Protein phosphorylation regulates protein function by inducing conformational changes, but whether they are further regulated before dephosphorylation was unknown. As a postdoc with Tony Hunter at Salk, Lu combined yeast genetic suppressor and protein-interaction screens for the mitotic kinase NIMA to clone human Pin1, the only essential prolyl isomerase in yeast (Nature 1996). Our lab at Harvard then discovered that Pin1 is the only known prolyl isomerase that can bind to and isomerize certain pSer/Thr-Pro motifs in a subset of proteins (Science 1997, 1999). We thus proposed that cis-trans prolyl isomerization catalytically regulates conformation and function after phosphorylation as a unique signaling mechanism, which is now shown to act a molecular timer to coordinate multiple pathways in diverse cellular processes.
Dr. Lu Laboratory and Dr. Zhou Laboratory, Western University, 1400 Western Road, SDRI Room 107, London, Ontario N6G 2V4, Canada. The co-crystal structures of Pin1 and its inhibitors are generated by Shaunik Sharma using Pymol.
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