Phosphorylation-specific prolyl isomerization: is there an underlying theme?
The prolyl isomerase Pin1 is a conserved enzyme that is intimately involved in diverse biological processes and pathological conditions such as cancer and Alzheimer's disease. By catalysing cis-trans interconversion of certain motifs containing phosphorylated serine or threonine residues followed by a proline residue (pSer/Thr-Pro), Pin1 can have profound effects on phosphorylation signalling. The structural and functional differences that result from cis-trans isomerization of specific pSer/Thr-Pro motifs probably underlie most, if not all, Pin1-dependent actions. Phosphorylation-dependent prolyl isomerization by Pin1 remains a unique mode for the modulation of signal transduction. Here, we provide an overview of the plethora of regulatory events that involve this unique enzyme, with a particular focus on oncogenic signalling and neurodegeneration.
Wulf
Gerburg
G
Cancer Biology Program, Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 77 Avenue Louis Pasteur, NRB 1030, Boston, MA 02115, USA. gwulf@bidmc.harvard.edu <gwulf@bidmc.harvard.edu>
Finn
Greg
G
Suizu
Futoshi
F
Lu
Kun Ping
KP
D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation; D006801:Humans; D007536:Isomerism; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D019696:Peptidylprolyl Isomerase / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism; D010769:Phosphothreonine / Q000378:metabolism; D011487:Protein Conformation; D015398:Signal Transduction / Q000502:physiology*
D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D010769:Phosphothreonine; D010768:Phosphoserine; C000606846:PIN1 protein, human; D019696:Peptidylprolyl Isomerase