Abstract
Mixed lineage kinase 3 (MLK3) is a MAP3K that activates the JNK-dependent MAPK pathways. Here, we show that MLK3 is required for cell migration in a manner independent of its role as a MAP3K or MLK3 kinase activity. Rather, MLK3 functions in a regulated way to limit levels of the activated GTPase Rho by binding to the Rho activator, p63RhoGEF/GEFT, which, in turn, prevents its activation by Galphaq. These findings demonstrate a scaffolding role for MLK3 in controlling the extent of Rho activation that modulates cell migration. Moreover, they suggest that MLK3 functions as a network hub that links a number of signaling pathways.
| Original language | English |
|---|---|
| Journal | Molecular Cell |
| Volume | 32 |
| Issue number | 1 |
| Pages (from-to) | 43-56 |
| Number of pages | 14 |
| ISSN | 1097-2765 |
| DOIs | |
| Publication status | Published - 10 Oct 2008 |
| Externally published | Yes |
Keywords
- Cell Line
- Cell Movement/physiology
- Cytoskeleton/ultrastructure
- Focal Adhesions/ultrastructure
- GTP-Binding Protein alpha Subunits, Gq-G11/metabolism
- Guanine Nucleotide Exchange Factors/metabolism
- Humans
- In Vitro Techniques
- MAP Kinase Kinase Kinases/antagonists & inhibitors
- MAP Kinase Signaling System
- Models, Biological
- Protein Binding
- Pseudopodia/ultrastructure
- RNA, Small Interfering/genetics
- Receptors, G-Protein-Coupled/metabolism
- Recombinant Fusion Proteins/metabolism
- Rho Guanine Nucleotide Exchange Factors
- Serum Response Factor/metabolism
- Signal Transduction
- rhoA GTP-Binding Protein/metabolism