p120-catenin is a binding partner and substrate for Group B Pak kinases.
Pak5 is a member of the Group B p21-activated kinases, which are effectors of the Rho family GTPases Cdc42 and Rac. Pak5 has been shown to promote cytoskeletal reorganization, inducing filopodia formation and neurite outgrowth in neuroblastoma cells. In this study, we used affinity chromatography followed by SDS-PAGE and mass spectrometry to identify potential downstream effectors of Pak5. Using this approach, we isolated p120-catenin (p120), a known regulator of cytoskeletal reorganization and Rho GTPases. Using co-immunoprecipitation assays we found that p120 preferentially interacts with Pak5 among the Group B Paks. Results from immunofluorescence studies revealed that Pak5 and p120 co-localize in cells. Both Pak5 and constitutively active Pak4, the founding member of the Group B Paks, directly phosphorylate p120 in vitro. The phosphorylation was shown by Western blot and immunofluorescence to take place specifically on serine 288. This study is the first report of an upstream serine/threonine kinase that phosphorylates p120.
Wong
Lisa Epstein
LE
Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology, Ernest Mario School of Pharmacy at Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854, USA.
Reynolds
Albert B
AB
Dissanayaka
Nadishani T
NT
Minden
Audrey
A
D000818:Animals; D001667:Binding, Competitive; D015153:Blotting, Western; D051177:Catenins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D051379:Mice; D008856:Microscopy, Fluorescence; D041681:NIH 3T3 Cells; D010766:Phosphorylation; D011485:Protein Binding; D012694:Serine / Q000378:metabolism; D013379:Substrate Specificity; D014162:Transfection; D054462:p21-Activated Kinases / Q000235:genetics / Q000378:metabolism*; D000095002:Delta Catenin
D051177:Catenins; D049452:Green Fluorescent Proteins; D012694:Serine; C116367:PAK4 protein, human; C443802:PAK5 protein, human; D054462:p21-Activated Kinases; D000095002:Delta Catenin