MLK3 limits activated Galphaq signaling to Rho by binding to p63RhoGEF

Research output: Contribution to journal › Journal article › Research › peer-review

  • Katherine I Swenson-Fields
  • Joshua C Sandquist
  • Jessica Rossol-Allison
  • Irene C Blat
  • Wennerberg, Krister
  • Keith Burridge
  • Anthony R Means

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 languageEnglish
JournalMolecular Cell
Volume32
Issue number1
Pages (from-to)43-56
Number of pages14
ISSN1097-2765
DOIs
Publication statusPublished - 10 Oct 2008
Externally publishedYes

    Research areas

  • 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

ID: 199432516