Subgroup II PAK-mediated phosphorylation regulates Ran activity during mitosis
| Type | Article | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| Date | 2010-09 | ||||||||
| Language | English | ||||||||
| 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. |
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| Source | Journal Of Cell Biology (0021-9525) (Rockefeller Univ Press), 2010-09 , Vol. 190 , N. 5 , P. 807-822 | ||||||||
| DOI | 10.1083/jcb.200912056 | ||||||||
| WOS© Times Cited | 34 | ||||||||
| 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. | ||||||||
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