CAP interacts with cytoskeletal proteins and regulates adhesion-mediated ERK activation and motility.
CAP/Ponsin belongs to the SoHo family of adaptor molecules that includes ArgBP2 and Vinexin. These proteins possess an N-terminal sorbin homology (SoHo) domain and three C-terminal SH3 domains that bind to diverse signaling molecules involved in a variety of cellular processes. Here, we show that CAP binds to the cytoskeletal proteins paxillin and vinculin. CAP localizes to cell-extracellular matrix (ECM) adhesion sites, and this process requires binding to vinculin. Overexpression of CAP induces the aggregation of paxillin, vinculin and actin at cell-ECM adhesion sites. Moreover, CAP inhibits adhesion-dependent processes such as cell spreading and focal adhesion turnover, whereas a CAP mutant that is unable to localize to cell-ECM adhesion sites is incapable of exerting these effects. Finally, depletion of CAP by siRNA-mediated knockdown leads to enhanced cell spreading, migration and the activation of the PAK/MEK/ERK pathway in REF52 cells. Taken together, these results indicate that CAP is a cytoskeletal adaptor protein involved in modulating adhesion-mediated signaling events that lead to cell migration.
Zhang
Mei
M
Department of Internal Medicine, Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA.
Liu
Jun
J
Cheng
Alan
A
Deyoung
Stephanie M
SM
Chen
Xiaowei
X
Dold
Lisa H
LH
Saltiel
Alan R
AR
D000818:Animals; D002448:Cell Adhesion; D002465:Cell Movement; D021982:Cell-Matrix Junctions; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D003598:Cytoskeletal Proteins / Q000502:physiology*; D004789:Enzyme Activation; D005109:Extracellular Matrix / Q000502:physiology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008840:Microfilament Proteins / Q000235:genetics / Q000502:physiology*; D009154:Mutation; D051419:Paxillin / Q000378:metabolism; D011485:Protein Binding; D015398:Signal Transduction; D016596:Vinculin / Q000378:metabolism
D003598:Cytoskeletal Proteins; D008840:Microfilament Proteins; D051419:Paxillin; C119201:ponsin; D016596:Vinculin; D048049:Extracellular Signal-Regulated MAP Kinases