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MLK3 limits activated Galphaq signaling to Rho by binding to p63RhoGEF

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

  • 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.

OriginalsprogEngelsk
TidsskriftMolecular Cell
Vol/bind32
Udgave nummer1
Sider (fra-til)43-56
Antal sider14
ISSN1097-2765
DOI
StatusUdgivet - 10 okt. 2008
Eksternt udgivetJa

ID: 199432516