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Originally published In Press as doi:10.1074/jbc.M105153200 on July 25, 2001

J. Biol. Chem., Vol. 276, Issue 39, 36397-36403, September 28, 2001
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Cleavage of Doublecortin-like Kinase by Calpain Releases an Active Kinase Fragment from a Microtubule Anchorage Domain*

Harold A. Burgess and Orly ReinerDagger

From the Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel

Doublecortin-like kinase (DCLK) is widely expressed in postmitotic neurons throughout the embryonic nervous system. DCLK consists of an N-terminal doublecortin domain, responsible for its localization to microtubules, and a C-terminal serine-threonine kinase domain. Here we report that DCLK is a physiological substrate for the cysteine protease calpain. Cleavage of DCLK by calpain severs the kinase domain from its microtubule anchorage domain and releases it into the cytoplasm. The isolated kinase domain retains catalytic activity and is structurally similar to CPG16, a second product of the DCLK gene expressed in the adult brain that lacks the doublecortin domain. We propose that in neurons cleavage of DCLK by calpain represents a calciumresponsive mechanism to regulate localization of the DCLK kinase domain.


* This work was supported in part by Human Frontier Science Program Grant RG283199, by the Minerva Foundation, Germany, by Volkswagon-Stiftung, and by U.S.-Israel Binational Science Foundation Grant 97-00014.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 Incumbent of the Aser Rothstein Career Development Chair in Genetic Diseases. To whom correspondence should be addressed. Tel.: 972-8-9342319; Fax: 972-8-9344108; E-mail: orly.reiner@weizmann. ac.il.


Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
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Copyright © 2001 by the American Society for Biochemistry and Molecular Biology.