Originally published In Press as doi:10.1074/jbc.M307065200 on July 11, 2003
J. Biol. Chem., Vol. 278, Issue 41, 40305-40316, October 10, 2003
Protein Kinase M
Synthesis from a Brain mRNA Encoding an Independent Protein Kinase C Catalytic Domain
IMPLICATIONS FOR THE MOLECULAR MECHANISM OF MEMORY*
A. Ivan Hernandez 
,
Nancy Blace ,
John F. Crary 
,
Peter A. Serrano ,
Michael Leitges ¶,
Jenny M. Libien ,
Gila Weinstein ,
Andrew Tcherapanov and
Todd Charlton Sacktor ||
From the
Departments of Physiology, Pharmacology, and Neurology, the Graduate Program in Neural and Behavioral Science, State University of New York Downstate Medical Center, Brooklyn, New York 11203 and ¶Max-Planck-Institut für Experimentelle Endokrinologie, Feodor-Lynen-Strasse 7, D-30625 Hannover, Germany
Protein kinase M
(PKM) is a newly described form of PKC that is necessary and sufficient for the maintenance of hippocampal long term potentiation (LTP) and the persistence of memory in Drosophila. PKM is the independent catalytic domain of the atypical PKC isoform and produces long term effects at synapses because it is persistently active, lacking autoinhibition from the regulatory domain of PKC. PKM has been thought of as a proteolytic fragment of PKC. Here we report that brain PKM is a new PKC isoform, synthesized from a PKM mRNA encoding a PKC catalytic domain without a regulatory domain. Multiple -specific antisera show that PKM is expressed in rat forebrain as the major form of in the near absence of full-length PKC. A PKC knockout mouse, in which the regulatory domain was disrupted and catalytic domain spared, still expresses brain PKM, indicating that this form of PKM is not a PKC proteolytic fragment. Furthermore, the distribution of brain PKM does not correlate with PKC mRNA but instead with an alternate RNA transcript thought incapable of producing protein. In vitro translation of this RNA, however, generates PKM of the same molecular weight as that in brain. Metabolic labeling of hippocampal slices shows increased de novo synthesis of PKM in LTP. Because PKM is a kinase synthesized in an autonomously active form and is necessary and sufficient for maintaining LTP, it serves as an example of a link coupling gene expression directly to synaptic plasticity.
Received for publication, July 2, 2003
* This work was supported by National Institutes of Health Grants MH057068 and MH53576 (to T. C. S.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
|| To whom correspondence should be addressed: Dept. of Pharmacology, Box 29, SUNY Downstate Medical Center, 450 Clarkson Ave., Brooklyn, NY 11203. Tel.: 718-270-3933; Fax: 718-270-8974; E-mail: tsacktor{at}downstate.edu.
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Copyright © 2003 by the American Society for Biochemistry and Molecular Biology.
