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 f unctions. Type I c-Abl has been shown to be involved in LPS-induced differe ntiation and Type IV c-Abl, apoptosis, Ran has recently been shown to be in volved 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-stimula ted lymphoid B cells, Type I c-Abl tyrosine kinase is inactive, whereas Typ e 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 de tectable in B cells of endotoxin-sensitive inbred mice but absent in B cell s of endotoxin-resistant mice. These findings therefore suggest that Type I c-Abl and Ran are important targets in lipopolysaccharide-induced biologic al responses of hematopoietic cells.