PAK interacts with NCK and MLK2 to regulate the activation of jun N-terminal kinase.
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.
Poitras
Luc
L
Cancer Research Centre and Department of Medical Biology, Laval University, Hôtel-Dieu de Quebec, 9 rue McMahon, G1R 2J6, Québec, QC, Canada.
Jean
Steve
S
Islam
Nazrul
N
Moss
Tom
T
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D019556:COS Cells; D004789:Enzyme Activation; D004815:Epidermal Growth Factor / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008954:Models, Biological; D015513:Oncogene Proteins / Q000378:metabolism* / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism* / Q000502:physiology; D014466:Ultraviolet Rays; D029867:Xenopus Proteins / Q000378:metabolism; D054462:p21-Activated Kinases
D048868:Adaptor Proteins, Signal Transducing; C078332:Nck protein; D015513:Oncogene Proteins; D029867:Xenopus Proteins; D004815:Epidermal Growth Factor; D017346:Protein Serine-Threonine Kinases; D054462:p21-Activated Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D020930:MAP Kinase Kinase Kinases; C490540:map3k10 protein, Xenopus