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Induction of Neurite Outgrowth through Contactin and Nr-CAM by Extracellular Regions of Glial Receptor Tyrosine Phosphatase β
Authors:Takeshi Sakurai   Marc Lustig   Moshe Nativ   John J. Hemperly   Joseph Schlessinger   Elior Peles     Martin Grumet
Affiliation:*Department of Pharmacology, New York University Medical Center, New York 10016; SUGEN, Inc., Redwood City, California 94063-4720; and §Becton Dickinson Research Center, Becton Dickinson and Company, P.O. Box 12016, Research Triangle Park, North Carolina 27709-2016
Abstract:Receptor protein tyrosine phosphatase β (RPTPβ) is expressed as soluble and receptor forms with common extracellular regions consisting of a carbonic anhydrase domain (C), a fibronectin type III repeat (F), and a unique region called S. We showed previously that a recombinant Fc fusion protein with the C domain (βC) binds to contactin and supports neuronal adhesion and neurite growth. As a substrate, βCFS was less effective in supporting cell adhesion, but it was a more effective promoter of neurite outgrowth than βCF. βS had no effect by itself, but it potentiated neurite growth when mixed with βCF. Neurite outgrowth induced by βCFS was inhibited by antibodies against Nr-CAM and contactin, and these cell adhesion molecules formed a complex that bound βCFS. NIH3T3 cells transfected to express βCFS on their surfaces induced neuronal differentiation in culture. These results suggest that binding of glial RPTPβ to the contactin/Nr-CAM complex is important for neurite growth and neuronal differentiation.
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