Nicholas Nicole S, Pipili Aikaterini, Lesjak Michaela S, Wells Claire M
a Division of Cancer Studies , New Hunts House, Guy's Campus, King's College London , London , UK.
b National Institute for Health Research (NIHR) Biomedical Research Centre, Guy's and St Thomas's Hospital and King's College London , London , UK.
Small GTPases. 2019 Jul;10(4):289-295. doi: 10.1080/21541248.2017.1295830. Epub 2017 Mar 17.
PAK1 and PAK4 are members of the p-21 activated kinase family of serine/threonine kinases. PAK1 has previously been implicated in both the formation and disassembly of invasive cell protrusions, termed invadopodia. We recently reported a novel role for PAK4 during invadopodia maturation and confirmed a specific role for PAK1 in invadopodia formation; findings we will review here. Moreover, we found that PAK4 induction of maturation is delivered via interaction with the RhoA regulator PDZ-RhoGEF. We can now reveal that loss of PAK4 expression leads to changes in invadopodia dynamics. Ultimately we propose that PAK4 but not PAK1 is a key mediator of RhoA activity and provide further evidence that modulation of PAK4 expression levels leads to changes in RhoA activity.
PAK1和PAK4是丝氨酸/苏氨酸激酶的p-21激活激酶家族成员。PAK1此前被认为与侵袭性细胞突起（称为侵袭伪足）的形成和分解有关。我们最近报道了PAK4在侵袭伪足成熟过程中的新作用，并证实了PAK1在侵袭伪足形成中的特定作用；我们将在此处回顾这些发现。此外，我们发现PAK4通过与RhoA调节剂PDZ-RhoGEF相互作用诱导成熟。我们现在可以揭示，PAK4表达缺失会导致侵袭伪足动力学发生变化。最终，我们提出PAK4而非PAK1是RhoA活性的关键介质，并提供了进一步的证据，即PAK4表达水平的调节会导致RhoA活性的变化。
