L-selectin tyrosine phosphorylates Cbl and induces association of tyrosine-phosphorylated Cbl with CrkL and Grb2

L-Selectin-mediated rolling of leukocytes on endothelial cells is an import ant step for lymphocyte homing and an early event in the immune response to pathogens or inflammatory stimuli. We have previously elucidated intracell ular signaling cascades upon L-selectin engagement resulting in activation of Has, Rac and JNK as well as cytoskeletal changes, oxygen release, cerami de synthesis and receptor capping. Activation of the src-tyrosine kinase p5 6lck is followed by phosphorylation of the L-selectin molecule and MAP-K. H ere we show a tyrosine kinase dependent phosphorylation of the Cbl adapter protein after L-selectin engagement in lymphocytes. Phosphorylation of Cbl was absent in Jurkat cells that are pharmacologically treated with tyrosine kinase inhibitors and in lck-deficient JCaM cells. There is an activation induced association of tyrosine phosphorylated Cbl with Grb2 and CrkL, resp ectively, but not CrkII. Therefore, the adapter protein Cbl plays a role in L-selectin signaling and might modulate immune function by the specific re cruitment of signaling molecules to multiprotein complexes. (C) 2001 Academ ic Press.