TYROSINE PHOSPHORYLATION OF L1 FAMILY ADHESION MOLECULES - IMPLICATION OF THE EPH KINASE CEK5

The L1 family comprises transmembrane cell adhesion molecules of the i mmunoglobulin superfamily that play an important role in neuronal migr ation and axon outgrowth, fasciculation, and myelination, Consistent w ith a crucial role in developmental processes, mutations in L1 cause s evere brain malformations, Although L1 activates intracellular signali ng pathways, little is known about the membrane proximal events of L1 signaling, The cytoplasmic domains of L1 family proteins contain sever al conserved tyrosine residues that are potential targets for receptor tyrosine kinases, Here, we report that the L1 family protein Ng-CAM i s phosphorylated on tyrosine in embryonic day 13 chicken retina. This is the first demonstration of in vivo tyrosine phosphorylation of an L 1-like molecule, Because chicken embryo kinase 5 (Cek5) is a receptor tyrosine kinase expressed in neuronal processes and activated in the c hicken embryonic retina, we have analyzed the possible role of Cek5 in L1 phosphorylation, The rat glioblastoma cell line B28 was stably tra nsfected with human L1, Additional transient transfection with Cek5 cD NA led to expression of Cek5 in its tyrosine-phosphorylated, activated form, Biochemical analysis revealed that L1 is phosphorylated on tyro sine in Cek5-transfected cells but not in control transfectants, Furth ermore, direct phosphorylation of the L1 cytoplasmic domain by Cek5 wa s demonstrated in an in vitro kinase assay. Tyrosine phosphorylation m ay represent a novel mechanism of signal cascade initiation through L1 . (C) 1997 Wiley-Liss, Inc.