title: Pinning down proline-directed phosphorylation signaling.
abstract: The reversible phosphorylation of proteins on serine or threonine residues preceding proline (Ser/Thr-Pro) is a major cellular signaling mechanism. Although it is proposed that phosphorylation regulates the function of proteins by inducing a conformational change, there are few clues about the actual conformational changes and their importance. Recent identification of the novel prolyl isomerase Pin1 that specifically isomerizes only the phosphorylated Ser/Thr-Pro bonds in certain proteins led us to propose a new signaling mechanism, whereby prolyl isomerization catalytically induces conformational changes in proteins following phosphorylation to regulate protein function. Emerging data indicate that such conformational changes have profound effects on catalytic activity, dephosphorylation, protein-protein interactions, subcellular location and/or turnover. Furthermore, this post-phosphorylation mechanism might play an important role in cell growth control and diseases such as cancer and Alzheimer's.
authors.affiliation: Cancer Biology Program, Division of Hematology/Oncology, Dept. of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, HIM 1047, Boston, MA 02215, USA. klu@caregroup.harvard.edu
authors.forename: Kun Ping
authors.initials: KP
authors.lastname: Lu
authors.forename: Yih Cherng
authors.initials: YC
authors.lastname: Liou
authors.forename: Xiao Zhen
authors.initials: XZ
authors.lastname: Zhou
mesh_terms: D000544:Alzheimer Disease / Q000201:enzymology; D020816:Amino Acid Motifs; D000818:Animals; D006801:Humans; D008958:Models, Molecular; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D009369:Neoplasms / Q000201:enzymology; D019696:Peptidylprolyl Isomerase / Q000378:metabolism / Q000502:physiology*; D010766:Phosphorylation; D011392:Proline / Q000502:physiology*; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D011506:Proteins; D011392:Proline; C000606846:PIN1 protein, human; D019696:Peptidylprolyl Isomerase