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Originally published In Press as doi:10.1074/jbc.C200434200 on August 20, 2002

J. Biol. Chem., Vol. 277, Issue 40, 36909-36912, October 4, 2002
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ACCELERATED PUBLICATION
The Motor Protein Kinesin-1 Links Neurofibromin and Merlin in a Common Cellular Pathway of Neurofibromatosis*

Mohamed-Ali HakimiDagger , David W. Speicher, and Ramin Shiekhattar§

From The Wistar Institute, Philadelphia, Pennsylvania 19104

Mutations in either of the two tumor suppressor genes NF1 (neurofibromin) and NF2 (merlin) result in Neurofibromatosis, a condition predisposing individuals to developing a variety of benign and malignant tumors of the central and peripheral nervous systems. Here we report the identification of two distinct NF1-containing complexes, one in the soluble and the other in the particulate fraction of HeLa extract. We show that the soluble NF1 complex delineates a large holo-NF1 complex (2 MDa) encompassing the components of a smaller particulate core-NF1 complex (400 kDa). Purification of the core-NF1 complex followed by mass spectrometric analysis revealed the motor protein, kinesin-1 heavy chain (HsuKHC/KIF5B), as a catalytic subunit of both NF-1-containing complexes. Importantly, although NF1 and NF2 are not in a stable association, NF2 is also a component of a distinct kinesin-1-containing complex. These results point to kinesin-1 as a common denominator between NF1 and NF2.


* The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Dagger Supported by a postdoctoral fellowship from Association pour la Recherche sur le Cancer (France).

§ Supported by National Institutes of Health Grants CA 90758-01 and ACS RSG-01-028-01-CNE. To whom correspondence should be addressed: The Wistar Inst., 3601 Spruce St., Philadelphia, PA 19104. Tel.: 215-898-3896; Fax: 215-898-3986; E-mail: shiekhattar@wistar.upenn.edu.


Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.


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