Disease relevance of PAK6

• Finally, we observe that autophosphorylated, active PAK6 protein is differently expressed among prostate cancer cell lines [1].
• PAK6 interaction provides a mechanism for cross-talk between steroid hormone receptors and Cdc42-mediated signal transduction pathways and could contribute to the effects of tamoxifen in breast cancer and in other tissues [2].

High impact information on PAK6

• A survey of currently known AR-binding proteins revealed the presence of an FXXFF motif in gelsolin and an FXXMF motif in PAK6 [3].
• Mutation of a consensus p38 MAP kinase target site at serine 165 decreased PAK6 kinase activity [4].
• Suppression does not depend upon GTPase binding to PAK6 and is not mimicked by the closely related PAK1 and PAK4 isoforms [1].
• PAK6 is a serine/threonine kinase belonging to the p21-activated kinase (PAK) family implicated in actin reorganization and cell motility, gene transcription, apoptosis, and cell transformation [1].
• PAK6 is a 75-kDa protein that contains a putative amino-terminal Cdc42/Rac interactive binding motif and a carboxyl-terminal kinase domain [5].

Biological context of PAK6

• The expression pattern of PAK5 is distinct from that of PAK4 and PAK6, suggesting a functional division among PAK-II subfamily kinases based on differential tissue distribution [6].
• Transient transfection experiments showed that PAK6 specifically repressed AR-mediated transcription [5].
• AR and ERalpha transcriptional activities were inhibited by PAK6 in transient transfections with episomal and integrated reporter genes [2].
• PAK5 inactivates MARK, not by phosphorylation, but by binding to the catalytic domain [7].

Anatomical context of PAK6

• Northern blot analysis revealed that PAK6 is highly expressed in testis and prostate tissues [5].
• Through deletion analysis we observed that the mitochondrial localization of PAK5 is controlled by multiple domains, providing evidence that the kinase activity of PAK5 is critical to its ability to cycle on and off mitochondria, and demonstrate that expression of kinase-inactive PAK5 elicits dramatic effects on mitochondrial morphology [8].
• PAK5 contributes to microtubule stability by preventing the MARK-induced phosphorylation of tau; conversely, PAK5 contributes to actin dynamics, presumably through the activation of cofilin, an F-actin severing protein [7].
• Thus, MARK and its regulators MARKK and PAK5 appear to mediate the crosstalk between the actin and microtubule cytoskeleton in an antagonistic fashion [7].

Associations of PAK6 with chemical compounds

• Most importantly, immunofluorescence studies showed that PAK6 cotranslocates into the nucleus with AR in response to androgen [5].
• PAK6 also bound to the ERalpha, and binding was enhanced by 4-hydroxytamoxifen [2].

Regulatory relationships of PAK6

• Kinase-dependent inhibition by PAK6 extended to the enhanced AR-mediated transcription seen in the presence of coactivating molecules and to the action of AR coinhibitors [1].

Other interactions of PAK6

• Mechanism of p21-activated kinase 6-mediated inhibition of androgen receptor signaling [1].
• Androgen receptor specifically interacts with a novel p21-activated kinase, PAK6 [5].

References