Subgroup II PAK-mediated phosphorylation regulates Ran activity during mitosis.
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Bompard G, Rabeharivelo G, Frank M, Cau J, Delsert C, Morin N
Subgroup II PAK-mediated phosphorylation regulates Ran activity during mitosis.
J Cell Biol. 2010 Sep 6;190(5):807-22. doi: 10.1083/jcb.200912056. Epub 2010 Aug 30.
- PubMed ID
- 20805321 [ View in PubMed]
- 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-bound 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.