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MLK3 limits activated Galphaq signaling to Rho by binding to p63RhoGEF.


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.

SUBMITTER: Swenson-Fields KI 

PROVIDER: S-EPMC2603627 | biostudies-literature | 2008 Oct

REPOSITORIES: biostudies-literature

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MLK3 limits activated Galphaq signaling to Rho by binding to p63RhoGEF.

Swenson-Fields Katherine I KI   Sandquist Joshua C JC   Rossol-Allison Jessica J   Blat Irene C IC   Wennerberg Krister K   Burridge Keith K   Means Anthony R AR  

Molecular cell 20081001 1


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 activatio  ...[more]

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