c-Abl-binding protein interacts with p21-activated kinase 2 (PAK-2) to regulate PDGF-induced membrane ruffles.
p21-Activated kinases (PAKs) are serine/threonine kinases involved in multiple cellular functions including cytoskeleton regulation, proliferation and apoptosis. We performed a screen for proteins interacting with PAK-2, a ubiquitously expressed kinase involved in apoptotic signaling. Among the PAK-2 interacting proteins were different members of the Abl-binding protein family. Abl-binding proteins bound to a proline-rich region of PAK-2 located in the regulatory N terminus. Moreover, active PAK-2 phosphorylated Abl-binding proteins in vitro. Interestingly, we show that PAK-2 also interacted with c-Abl but via a different domain than with the Abl-binding proteins. PAK-2 and Abi-1 co-localized in the cytoplasm and to membrane dorsal ruffles induced by PDGF treatment. Expression of mutant PAK-2 deficient in binding to Abl-binding proteins or silencing of PAK-2 expression prevented the formation of membrane dorsal ruffles in response to PDGF. Our findings define a new class of PAK-interacting proteins, which play an important role in actin cytoskeletal reorganization.
Machuy
Nikolaus
N
Max Planck Institute for Infection Biology, Department of Molecular Biology, Charitéplatz 1, D-10117 Berlin, Germany.
Campa
Fanny
F
Thieck
Oliver
O
Rudel
Thomas
T
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects* / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D016315:Proto-Oncogene Proteins c-abl / Q000235:genetics / Q000378:metabolism*; D054462:p21-Activated Kinases
D048868:Adaptor Proteins, Signal Transducing; D003598:Cytoskeletal Proteins; D010982:Platelet-Derived Growth Factor; D016315:Proto-Oncogene Proteins c-abl; C515907:PAK2 protein, human; C515909:Pak2 protein, mouse; D017346:Protein Serine-Threonine Kinases; D054462:p21-Activated Kinases