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FEBS Lett. 2003 May 22;543(1-3):129-35.

PAK interacts with NCK and MLK2 to regulate the activation of jun N-terminal kinase.

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Cancer Research Centre and Department of Medical Biology, Laval University, Hôtel-Dieu de Quebec, 9 rue McMahon, G1R 2J6, Québec, QC, Canada.


The p21-GTPase activated kinase, PAK1, and the mixed lineage kinase, MLK2, have been implicated in the activation of jun N-terminal kinase (JNK). However, the role of PAK1 in JNK activation is still not understood. Here we show that over-expression of the SH3-SH2 adapter Nck 'squelches' JNK activation but this squelching is relieved by over-expression of PAK1. In turn, PAK1 squelches activation of JNK by MLK2 and these kinases interact via their catalytic domains. The data suggest that PAK1 recruits MLK2 to an activated receptor via the adapter Nck, but cannot itself induce activation of the JNK cascade.

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