L1 AND N-CAM ANTIBODIES TRIGGER PROTEIN PHOSPHATASE-ACTIVITY IN GROWTH CONE-ENRICHED MEMBRANES

Triggering of the cell adhesion molecules L1 or N-CAM in a nerve growt h cone membrane fraction from fetal rat brain with purified L1 or N-CA M or specific antibodies decreases the steady-state levels of protein tyrosine phosphorylation in the membranes. Here we report that trigger ing of L1 and N-CAM in the growth cone-enriched membrane fraction with a subset of antibodies directed against the extracellular region of L 1 and N-CAM elicited dephosphorylation of endogenous protein substrate s, indicating the presence of a cell adhesion molecule-activated phosp hatase. The most prominent substrates were a membrane-associated 200-k Da protein and tubulin, both of which were dephosphorylated on tyrosin e and serine/threonine residues in response to L1 or N-CAM triggering. The antibody-induced phosphatase was inhibited by agents that blocked tyrosine and serine/threonine phosphatases, including sodium orthovan adate, vanadyl sulfate, zinc cations, heparin, and sodium pyrophosphat e. Purified L1 and N-CAM fragments and other antibodies reacting with the extracellular region of these adhesion molecules did not activate the phosphatase but did inhibit tyrosine phosphorylation, These proper ties suggested that triggering of L1 and N-CAM can lead to either phos phatase activation or tyrosine kinase inhibition in growth cone membra nes. These findings implicate protein phosphatases in addition to tyro sine kinases as components of LI and N-CAM intracellular signaling pat hways in growth cones.