title: Phosphorylation of cortactin by p21-activated kinase.
abstract: Cortactin is an F-actin binding protein that is enriched in dynamic cytoskeletal organelles such as podosomes, membrane ruffles, and lamellipodia. We have shown previously that Src-phosphorylation of cortactin is not required for its translocation to phorbol-ester induced podosomes in A7r5 aortic smooth muscle cells, but may be important for stability and turnover of podosomes. However, little is known of the role of Ser/Thr kinases in the regulation of cortactin. Here, we report that p21-associated kinase (PAK), which plays a crucial role in the formation of podosome and membrane ruffles, is able to phosphorylate cortactin in vitro. The predominant phosphorylation site is located at Ser113 in the first actin-binding repeat. Phosphorylation by PAK is not required for the translocation of cortactin to podosomes, lamellipodia, or membrane ruffles in A7r5 smooth muscle cells. However, binding of cortactin to F-actin is significantly reduced by PAK-phosphorylation. Taken together, these results suggest a role for PAK-phosphorylation of cortactin in the regulation of the dynamics of branched actin filaments in dynamic cytoskeletal organelles.
authors.affiliation: Department of Biochemistry and Protein Function Discovery Program, Queen's University, Kingston, Ont., Canada K7L 3N6.
authors.forename: Bradley A
authors.initials: BA
authors.lastname: Webb
authors.forename: Shutang
authors.initials: S
authors.lastname: Zhou
authors.forename: Robert
authors.initials: R
authors.lastname: Eves
authors.forename: Linda
authors.initials: L
authors.lastname: Shen
authors.forename: Lilly
authors.initials: L
authors.lastname: Jia
authors.forename: Alan S
authors.initials: AS
authors.lastname: Mak
mesh_terms: D000818:Animals; D001665:Binding Sites; D002478:Cells, Cultured; D051356:Cortactin / Q000737:chemistry* / Q000378:metabolism*; D004789:Enzyme Activation; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry* / Q000378:metabolism*; D051381:Rats; D054462:p21-Activated Kinases
chemical_list: D051356:Cortactin; C515906:Pak1 protein, rat; D017346:Protein Serine-Threonine Kinases; D054462:p21-Activated Kinases