We have shown that Cdc42 directly regulates PAK4 activity in mammalian cells through an auto-inhibitory domain (AID) that binds in a manner similar to pseudosubstrates 13, 14. The structural basis for PAK4’s preference for serine containing substrate sites has recently been elucidated 12. PAK4 is a kinase with strong links to cellular transformation and cancer metastasis, as reviewed 11. The loss of PAK4 prevents proper polarization and thus formation of the endothelial lumen 9, consistent with defects seen in PAK4−/− mice 10. The phenotype of PAK4-null mice, which is embryonic lethal, involves defects in the fetal heart as well as in neuronal development and axonal outgrowth 8. This is consistent with PAK4 functioning primarily at cell–cell contacts in mammalian cells 6, with Cdc42 also being required for adherent junction formation 7. PAK4-like kinases are ubiquitously expressed in metazoans but are not found in protozoa or fungi 4, 5. Any unused portion of a free-trial period will be forfeited when the user purchases a subscription.īy using our app, you accept our Privacy Policy and Terms of use.Mammalian PAK isoforms are categorized into two groups on the basis of their structural and biochemical features: the conventional or group I PAKs in human comprise PAKs1–3, whereas the group II PAKs (PAK4–6) are encoded by three genes in mammals 1, 2, 3. However, you are not able to cancel the current subscription during its active period You may turn off the auto-renewal of your subscription via your iTunes Account Settings.
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