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http://purl.uniprot.org/citations/8805275http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/8805275http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/8805275http://www.w3.org/2000/01/rdf-schema#comment"

Background

The Rho-related GTP-binding proteins Cdc42 and Rac1 have been shown to regulate signaling pathways involved in cytoskeletal reorganization and stress-responsive JNK (Jun N-terminal kinase) activation. However, to date, the GTPase targets that mediate these effects have not been identified. PAK defines a growing family of mammalian kinases that are related to yeast Ste20 and are activated in vitro through binding to Cdc42 and Rac1 (PAK: p21 Cdc42-/Rac-activated kinase). Clues to PAK function have come from studies of Ste20, which controls the activity of the yeast mating mitogen-activated protein (MAP) kinase cascade, in response to a heterotrimeric G protein and Cdc42.

Results

To initiate studies of mammalian Ste20-related kinases, we identified a novel human PAK isoform, hPAK1. When expressed in yeast, hPAK1 was able to replace Ste20 in the pheromone response pathway. Chemical mutagenesis of a plasmid encoding hPAK1, followed by transformation into yeast, led to the identification of a potent constitutively active hPAK1 with a substitution of a highly conserved amino-acid residue (L107F) in the Cdc42-binding domain. Expression of the hPAK1(L107F) allele in mammalian cells led to specific activation of the Jun N-terminal kinase MAP kinase pathway, but not the mechanistically related extracellular signal-regulated MAP kinase pathway.

Conclusions

These results demonstrate that hPAK1 is a GTPase effector controlling a downstream MAP kinase pathway in mammalian cells, as Ste20 does in yeast. Thus, PAK and Ste20 kinases play key parts in linking extracellular signals from membrane components, such as receptor-associated G proteins and Rho-related GTPases, to nuclear responses, such as transcriptional activation."xsd:string
http://purl.uniprot.org/citations/8805275http://purl.org/dc/terms/identifier"doi:10.1016/s0960-9822(02)00546-8"xsd:string
http://purl.uniprot.org/citations/8805275http://purl.org/dc/terms/identifier"doi:10.1016/s0960-9822(02)00546-8"xsd:string
http://purl.uniprot.org/citations/8805275http://purl.uniprot.org/core/author"Brown J.L."xsd:string
http://purl.uniprot.org/citations/8805275http://purl.uniprot.org/core/author"Brown J.L."xsd:string
http://purl.uniprot.org/citations/8805275http://purl.uniprot.org/core/author"Baer M."xsd:string
http://purl.uniprot.org/citations/8805275http://purl.uniprot.org/core/author"Baer M."xsd:string
http://purl.uniprot.org/citations/8805275http://purl.uniprot.org/core/author"Stowers L."xsd:string
http://purl.uniprot.org/citations/8805275http://purl.uniprot.org/core/author"Stowers L."xsd:string
http://purl.uniprot.org/citations/8805275http://purl.uniprot.org/core/author"Chant J."xsd:string
http://purl.uniprot.org/citations/8805275http://purl.uniprot.org/core/author"Chant J."xsd:string
http://purl.uniprot.org/citations/8805275http://purl.uniprot.org/core/author"Trejo J."xsd:string
http://purl.uniprot.org/citations/8805275http://purl.uniprot.org/core/author"Trejo J."xsd:string
http://purl.uniprot.org/citations/8805275http://purl.uniprot.org/core/author"Coughlin S."xsd:string
http://purl.uniprot.org/citations/8805275http://purl.uniprot.org/core/author"Coughlin S."xsd:string
http://purl.uniprot.org/citations/8805275http://purl.uniprot.org/core/date"1996"xsd:gYear
http://purl.uniprot.org/citations/8805275http://purl.uniprot.org/core/date"1996"xsd:gYear
http://purl.uniprot.org/citations/8805275http://purl.uniprot.org/core/name"Curr. Biol."xsd:string
http://purl.uniprot.org/citations/8805275http://purl.uniprot.org/core/name"Curr. Biol."xsd:string
http://purl.uniprot.org/citations/8805275http://purl.uniprot.org/core/pages"598-605"xsd:string
http://purl.uniprot.org/citations/8805275http://purl.uniprot.org/core/pages"598-605"xsd:string
http://purl.uniprot.org/citations/8805275http://purl.uniprot.org/core/title"Human Ste20 homologue hPAK1 links GTPases to the JNK MAP kinase pathway."xsd:string
http://purl.uniprot.org/citations/8805275http://purl.uniprot.org/core/title"Human Ste20 homologue hPAK1 links GTPases to the JNK MAP kinase pathway."xsd:string
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