|Author(s)||Bompard Guillaume1, 2, 4, Rabeharivelo Gabriel1, 2, 4, Frank Marie1, 2, 4, Cau Julien1, 3, 4, Delsert Claude1, 2, 4, 5, Morin Nathalie1, 2, 4|
|Affiliation(s)||1 : Univ Montpellier 2, IFR 122, F-34293 Montpellier, France.
2 : CNRS, Ctr Rech Biochim Macromol, F-34293 Montpellier, France.
3 : CNRS, UPR 1142, Inst Human Genet, F-34396 Montpellier, France.
4 : Univ Montpellier 1, IFR 122, F-34293 Montpellier, France.
5 : IFREMER, Lab Genet & Pathol, F-17390 La Tremblade, France.
|Source||Journal Of Cell Biology (0021-9525) (Rockefeller Univ Press), 2010-09 , Vol. 190 , N. 5 , P. 807-822|
|WOS© Times Cited||27|
|Abstract||Ran is an essential GTPase that controls nucleocytoplasmic transport, mitosis, and nuclear envelope formation. These functions are regulated by interaction of Ran with different partners, and by formation of a Ran-GTP gradient emanating from chromatin. Here, we identify a novel level of Ran regulation. We show that Ran is a substrate for p21-activated kinase 4 (PAK4) and that its phosphorylation on serine-135 increases during mitosis. The endogenous phosphorylated Ran and active PAK4 dynamically associate with different components of the microtubule spindle during mitotic progression. A GDP-ound Ran phosphomimetic mutant cannot undergo RCC1-mediated GDP/GTP exchange and cannot induce microtubule asters in mitotic Xenopus egg extracts. Conversely, phosphorylation of GTP-bound Ran facilitates aster nucleation. Finally, phosphorylation of Ran on serine-135 impedes its binding to RCC1 and RanGAP1. Our study suggests that PAK4-mediated phosphorylation of GDP- or GTP-bound Ran regulates the assembly of Ran-dependent complexes on the mitotic spindle.|
Bompard Guillaume, Rabeharivelo Gabriel, Frank Marie, Cau Julien, Delsert Claude, Morin Nathalie (2010). Subgroup II PAK-mediated phosphorylation regulates Ran activity during mitosis. Journal Of Cell Biology, 190(5), 807-822. Publisher's official version : https://doi.org/10.1083/jcb.200912056 , Open Access version : https://archimer.ifremer.fr/doc/00014/12502/