LIGANDS FOR EPH-RELATED RECEPTOR TYROSINE KINASES THAT REQUIRE MEMBRANE ATTACHMENT OR CLUSTERING FOR ACTIVITY

The EPH-related transmembrane tyrosine kinases constitute the largest known family of receptor-like tyrosine kinases, with many members disp laying specific patterns of expression in the developing and adult ner vous system. A family of cell surface-bound ligands exhibiting distinc t, but overlapping, specificities for these EPH-related kinases was id entified. These ligands were unable to act as conventional soluble fac tors. However, they did function when presented in membrane-bound form , suggesting that they require direct cell-to-cell contact to activate their receptors. Membrane attachment may serve to facilitate ligand d imerization or aggregation, because antibody-mediated clustering activ ated previously inactive soluble forms of these ligands.