Calyculin A-induced Vimentin Phosphorylation Sequesters 14-3-3 and Displaces Other 14-3-3 Partners in Vivo
MetadataShow full item record
CitationTzivion, Guri, Zhi-Jun Luo, and Joseph Avruch. 2000. “Calyculin A-Induced Vimentin Phosphorylation Sequesters 14-3-3 and Displaces Other 14-3-3 Partnersin Vivo.” Journal of Biological Chemistry 275 (38): 29772–78. https://doi.org/10.1074/jbc.m001207200.
Abstract14-3-3 proteins bind their targets through a specific serine/threonine-phosphorylated motif present on the target protein. This binding is a crucial step in the phosphorylation-dependent regulation of various key proteins involved in signal transduction and cell cycle control, We report that treatment of COS-7 cells with the phosphatase inhibitor calyculin A induces association of 14-3-3 with a 55-kDa protein, identified as the intermediate filament protein vimentin, Association of vimentin with 14-3-3 depends on vimentin phosphorylation and requires the phosphopeptide-binding domain of 14-3-3, The region necessary for binding to 14-3-3 is confined to the vimentin amino-terminal head domain (amino acids 1-96). Monomeric forms of 14-3-3 do not bind vimentin in vivo or in vitro, indicating that a stable complex requires the binding of a 14-3-3 dimer to two sites on a single vimentin polypeptide. The calyculin A-induced association of vimentin with 14-3-3 in vivo results in the displacement of most other 14-3-3 partners, including the protooncogene Raf, which nevertheless remain capable of binding 14-3-3 in vitro, Concomitant with 14-3-3 displacement, calyculin A treatment blocks Raf activation by EGF; however, this inhibition is completely overcome by 14-3-3 overexpression in vivo or by the addition of prokaryotic recombinant 14-3-3 in vitro, Thus, phosphovimentin, by sequestering 14-3-3 and limiting its availability to other target proteins can affect intracellular signaling processes that require 14-3-3.
Citable link to this pagehttp://nrs.harvard.edu/urn-3:HUL.InstRepos:41482968
- HMS Scholarly Articles