title: A new strategy for caging proteins regulated by kinases.
abstract: A strategy has been developed for caging proteins that are endogenously regulated by phosphorylation. A key phosphorylatable serine in cofilin, an F-actin cleaving protein, was replaced with a nonphosphorylatable cysteine. The latter conversion ensures that the protein is no longer regulated by endogenous protein kinases. The cysteine residue was subsequently covalently modified with a negatively charged caging moiety, which electrostatically mimics the natural serine phosphate present in the inactive wild-type protein. Photoremoval of the cage generates an active protein, which cannot be switched off by endogenous protein kinases. Caged cofilin, and its irradiated counterpart, display the anticipated F-actin depolymerization and severing activities.
authors.affiliation: Department of Anatomy and Structural Biology, The Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
authors.forename: Mousumi
authors.initials: M
authors.lastname: Ghosh
authors.forename: Ilia
authors.initials: I
authors.lastname: Ichetovkin
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Song
authors.forename: John S
authors.initials: JS
authors.lastname: Condeelis
authors.forename: David S
authors.initials: DS
authors.lastname: Lawrence
mesh_terms: D051339:Actin Depolymerizing Factors; D000199:Actins / Q000737:chemistry / Q000378:metabolism*; D054461:Lim Kinases; D008840:Microfilament Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed; D010766:Phosphorylation; D011494:Protein Kinases / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction; D013329:Structure-Activity Relationship
chemical_list: D051339:Actin Depolymerizing Factors; D000199:Actins; D008840:Microfilament Proteins; D011494:Protein Kinases; D054461:Lim Kinases