Specific association of Type I c-Abl with Ran GTPase in lipopolysaccharide-mediated differentiation.
Each of several isoforms of c-Abl may be involved in different biological functions. Type I c-Abl has been shown to be involved in LPS-induced differentiation and Type IV c-Abl, apoptosis. Ran has recently been shown to be involved in LPS endotoxin signal transduction. Here we show that Type I c-Abl associates with Ran. Formation of this complex is specific, as Ran did not associate with the highly homologous Type IV c-Abl isoform. In non-stimulated lymphoid B cells, Type I c-Abl tyrosine kinase is inactive, whereas Type IV kinase is active. Formation of Type I c-Abl/Ran complex and activation of Type I c-Abl kinase activity are LPS dose-dependent. This complex is detectable in B cells of endotoxin-sensitive inbred mice but absent in B cells of endotoxin-resistant mice. These findings therefore suggest that Type I c-Abl and Ran are important targets in lipopolysaccharide-induced biological responses of hematopoietic cells.
Daniel
R
R
Department of Pathology and Laboratory Medicine, Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, Pennsylvania, PA 19140, USA.
Chung
S W
SW
Eisenstein
T K
TK
Sultzer
B M
BM
Wong
P M
PM
D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000201:enzymology / Q000276:immunology; D001483:Base Sequence; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D004789:Enzyme Activation; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008809:Mice, Inbred C3H; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000494:pharmacology; D011233:Precipitin Tests; D020033:Protein Isoforms; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D016315:Proto-Oncogene Proteins c-abl / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D020931:ran GTP-Binding Protein
D008070:Lipopolysaccharides; D016376:Oligonucleotides, Antisense; D020033:Protein Isoforms; D011505:Protein-Tyrosine Kinases; D016315:Proto-Oncogene Proteins c-abl; D020558:GTP Phosphohydrolases; D020931:ran GTP-Binding Protein