Signaling, regulation and specificity of the type II p21-activated kinases [Protein Structure and Folding]

April 8th, 2015 by Ha, B. H., Morse, E. M., Turk, B. E., Boggon, T. J.

The p21-activated kinases (PAKs) are a family of 6 serine-threonine kinases that act as key effectors of RHO family GTPases in mammalian cells. PAKs are subdivided into two groups: type I PAKs (PAK1, PAK2 and PAK3) and type II PAKs (PAK4, PAK5 and PAK6). While involved in common signaling pathways, recent work indicates that the two groups have distinct modes of regulation and have both unique and common substrates. Here, we review recent insights into the molecular level details that govern regulation of type II PAK signaling. We also consider mechanisms by which signal transduction is regulated at the level of substrate specificity. Finally, we discuss the implications of these studies for clinical targeting of these kinases.