PAKs in Human Disease

The p21-activated kinases (PAKs) are one of the first direct kinase targets of Ras-related small GTPases to be discovered and have emerged as central players in growth factor signaling networks that regulate morphogenetic processes. In some situations, PAKs control cell proliferation, but their wider role involves establishing cell polarity and promoting cellular plasticity via changes in the actin cytoskeleton. PAKs have been shown to impact on three important areas of human health, namely, cancer, brain function, and virus infection. We review the mechanisms and targets of PAKs in these contexts and provide an overview of the ways in which inhibitors might act to arrest tumor growth, combat virus infection, and promote cell apoptosis. Although PAKs are most abundant in the brain, there are few details of how they might be operating in this context. The advent of new and more selective PAK inhibitors promises new avenues of treatment and allows us to probe in greater detail the importance of PAK biology.