Brain armadillo protein delta-catenin interacts with Abl tyrosine kinase and modulates cellular morphogenesis in response to growth factors.
delta-Catenin associates with adhesive junctions and facilitates cellular morphogenesis (Lu et al., 1999). Here we show that delta-catenin colocalizes with actin filaments and Abl tyrosine kinase in the growth cones of cultured hippocampal neurons. PC12 cells induced to express delta-catenin show accelerated neurite extension upon nerve growth factor (NGF) stimulation. STI571, an Abl family kinase inhibitor, further accentuates these stimulatory effects. delta-Catenin is a potent substrate for Abl in vitro using an immunocomplex assay and most of the Abl-induced tyrosine phosphorylation within cells is present in the N-terminus of delta-catenin. When delta-catenin-expressing epithelial cells are induced to scatter in response to hepatocyte growth factor (HGF), STI571 leads to the rapid redistribution of delta-catenin and changes in cellular morphology. We suggest that delta-catenin is a possible Abl substrate and acts downstream of Abl to orchestrate actin-based cellular morphogenesis.
Lu
Q
Q
Center for Neurologic Diseases, Brigham and Women's Hospital, Boston, Massachusetts, USA. luq@mail.ecu.edu
Mukhopadhyay
N K
NK
Griffin
J D
JD
Paredes
M
M
Medina
M
M
Kosik
K S
KS
D008841:Actin Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D051186:Armadillo Domain Proteins; D001921:Brain / Q000166:cytology / Q000196:embryology* / Q000201:enzymology*; D051177:Catenins; D015815:Cell Adhesion Molecules; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005333:Fetus; D020439:Growth Cones / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D006133:Growth Substances / Q000494:pharmacology*; D007150:Immunohistochemistry; D051379:Mice; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D016716:PC12 Cells; D010750:Phosphoproteins; D010766:Phosphorylation / Q000187:drug effects; D016315:Proto-Oncogene Proteins c-abl / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D000095002:Delta Catenin
D051186:Armadillo Domain Proteins; D051177:Catenins; D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; D004791:Enzyme Inhibitors; D006133:Growth Substances; D019384:Nucleic Acid Synthesis Inhibitors; D010750:Phosphoproteins; D016315:Proto-Oncogene Proteins c-abl; D000095002:Delta Catenin