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J. Cell Biol.
© The Rockefeller University Press
0021-9525/97/02/907/12 $2.00
Volume 136, Number 4, February 24, 1997 907-918

Induction of Neurite Outgrowth through Contactin and Nr-CAM by Extracellular Regions of Glial Receptor Tyrosine Phosphatase beta

Takeshi Sakurai,* Marc Lustig,* Moshe Nativ,Dagger John J. Hemperly,§ Joseph Schlessinger,* Elior Peles,Dagger and Martin Grumet*

* Department of Pharmacology, New York University Medical Center, New York 10016; Dagger  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

Receptor protein tyrosine phosphatase beta  (RPTPbeta ) 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 (beta C) binds to contactin and supports neuronal adhesion and neurite growth. As a substrate, beta CFS was less effective in supporting cell adhesion, but it was a more effective promoter of neurite outgrowth than beta CF. beta S had no effect by itself, but it potentiated neurite growth when mixed with beta CF. Neurite outgrowth induced by beta CFS was inhibited by antibodies against Nr-CAM and contactin, and these cell adhesion molecules formed a complex that bound beta CFS. NIH3T3 cells transfected to express beta CFS on their surfaces induced neuronal differentiation in culture. These results suggest that binding of glial RPTPbeta to the contactin/Nr-CAM complex is important for neurite growth and neuronal differentiation.


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