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.