title: Protein kinase D-mediated phosphorylation at Ser99 regulates localization of p21-activated kinase 4.
abstract: PAKs (p21-activated kinases) are effectors of RhoGTPases. PAK4 contributes to regulation of cofilin at the leading edge of migrating cells through activation of LIMK (Lin-11/Isl-1/Mec-3 kinase). PAK4 activity is regulated by an autoinhibitory domain that is released upon RhoGTPase binding as well as phosphorylation at Ser474 in the activation loop of the kinase domain. In the present study, we add another level of complexity to PAK4 regulation by showing that phosphorylation at Ser99 is required for its targeting to the leading edge. This phosphorylation is mediated by PKD1 (protein kinase D1). Phosphorylation of PAK4 at Ser99 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.
authors.affiliation: *Department of Cancer Biology, Mayo Clinic Comprehensive Cancer Center, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, U.S.A.
authors.forename: Ligia I
authors.initials: LI
authors.lastname: Bastea
authors.forename: Heike
authors.initials: H
authors.lastname: Döppler
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Pearce
authors.forename: Nisha
authors.initials: N
authors.lastname: Durand
authors.forename: Samantha J
authors.initials: SJ
authors.lastname: Spratley
authors.forename: Peter
authors.initials: P
authors.lastname: Storz
mesh_terms: D048948:14-3-3 Proteins / Q000378:metabolism; D002465:Cell Movement; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D012694:Serine / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection; D054462:p21-Activated Kinases / Q000032:analysis* / Q000378:metabolism*
chemical_list: D048948:14-3-3 Proteins; D012694:Serine; C116367:PAK4 protein, human; C089212:protein kinase D; D054462:p21-Activated Kinases; D011493:Protein Kinase C