![]()
|
|
||||||||
J. Biol. Chem., Vol. 276, Issue 39, 36397-36403, September 28, 2001
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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.
Cleavage of Doublecortin-like Kinase by Calpain Releases an
Active Kinase Fragment from a Microtubule Anchorage 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.
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.
This article has been cited by other articles:
![]() |
A. M. Edelman, W.-Y. Kim, D. Higgins, E. G. Goldstein, M. Oberdoerster, and W. Sigurdson Doublecortin Kinase-2, a Novel Doublecortin-related Protein Kinase Associated with Terminal Segments of Axons and Dendrites J. Biol. Chem., March 4, 2005; 280(9): 8531 - 8543. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. E. GOLL, V. F. THOMPSON, H. LI, W. WEI, and J. CONG The Calpain System Physiol Rev, July 1, 2003; 83(3): 731 - 801. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. A. Burgess and O. Reiner Alternative Splice Variants of Doublecortin-like Kinase Are Differentially Expressed and Have Different Kinase Activities J. Biol. Chem., May 10, 2002; 277(20): 17696 - 17705. [Abstract] [Full Text] [PDF] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |