Protein Kinase D-mediated phosphorylation at serine 99 regulates localization of p21-activated kinase 4

p21-activated kinases (PAKs) are effectors of RhoGTPases. PAK4 contributes to regulation of cofilin at the leading edge of migrating cells through activation of Lin-11/Isl-1/Mec-3 kinase (LIMK). PAK4 activity is regulated by an autoinhibitory domain that is released upon RhoGTPase binding as well as phosphorylation at serine 474 in the activation loop of the kinase domain. We here add another level of complexity to PAK4 regulation by showing that phosphorylation at serine residue 99 is required for its targeting to the leading edge. This phosphorylation is mediated by protein kinase D1 (PKD1). Phosphorylation of PAK4 at S99 also mediates binding to 14-3-3 protein, and is required for the formation of a PAK4/LIMK/PKD1 complex that regulates cofilin activity and directed cell migration.

Source: BJ Cell - July 10, 2013 Category: Biochemistry Authors: L I Bastea, H Doppler, S E Pearce, N Durand, S J Spratley, P Storz Tags: BJ Signal Source Type: research