HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 279, Issue 52, 53932-53936, December 24, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/52/53932    most recent M408467200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Rosales, J. L. Articles by Lee, K.-Y. Search for Related Content PubMed PubMed Citation Articles by Rosales, J. L. Articles by Lee, K.-Y. Social Bookmarking                      What's this?

GTP-dependent Secretion from Neutrophils Is Regulated by Cdk5^*

Jesusa L. Rosales, Joel D. Ernst¶, Janice Hallows||, and Ki-Young Lee**

From the Department of Cell Biology and Anatomy, Cancer Biology and Neuroscience Research Groups, The University of Calgary, Calgary, Alberta T2N 4N1, Canada, ^||Department of Pathology, University of Washington, Seattle, Washington 98195, and ^¶Department of Medicine, New York University School of Medicine, New York, New York 10016

We have previously shown evidence for the existence of a calcium-independent, GTP-regulated mechanism of secretion from neutrophils, but this secretory mechanism remains to be fully elucidated. Cyclin-dependent kinase 5 (Cdk5), the various substrates of which include Munc18 and synapsin 1, has been implicated in neuronal secretion. Although the Cdk5 activator, p35, and Cdk5-p35 activity are primarily associated with neurons, we report here that p35 also exists in neutrophils and that an active Cdk5-p35 complex is present in these cells. Cdk5-p35 activity in human neutrophils is mostly localized in secretory granules, which show an increase in Cdk5-p35 level and activity upon GTP stimulation. The potent Cdk5 inhibitor, roscovitine, completely blocks GTP-stimulated granule Cdk5 activity, which accompanies lactoferrin secretion from neutrophil-specific granules. Roscovitine also inhibits GTP-induced lactoferrin secretion and surface localization of the secretion markers, CD63 and CD66b, to a certain extent. Furthermore, neutrophils from wild-type mice treated with roscovitine and neutrophils from p35^–/– mice exhibit comparable surface expression levels of both CD63 and CD66b upon GTP stimulation. Although our data suggest that other molecules control GTP-induced secretion from neutrophils, it is clear that Cdk5-p35 is required to elicit the maximum GTP-induced secretory response. Our observation that multiple proteins in neutrophil granules serve as specific substrates of Cdk5 further supports the premise that the kinase is a key component of the GTP-regulated secretory apparatus in neutrophils.

Received for publication, July 26, 2004 , and in revised form, October 4, 2004.

^* This study was supported in part by a University Research grant (to J. L. R. and K.-Y. L.) and an operating grant from the Canadian Institutes of Health Research (to K.-Y. L.). 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.

^** Alberta Heritage Foundation for Medical Research Senior Scholar.

To whom correspondence should be addressed. Tel.: 403-220-2882; Fax: 403-270-0834; E-mail: rosales{at}ucalgary.ca.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				M. Taniguchi, M. Taoka, M. Itakura, A. Asada, T. Saito, M. Kinoshita, M. Takahashi, T. Isobe, and S.-i. Hisanaga Phosphorylation of Adult Type Sept5 (CDCrel-1) by Cyclin-dependent Kinase 5 Inhibits Interaction with Syntaxin-1 J. Biol. Chem., March 16, 2007; 282(11): 7869 - 7876. [Abstract] [Full Text] [PDF]

				S. Maier, G. Staffler, A. Hartmann, J. Hock, K. Henning, K. Grabusic, R. Mailhammer, R. Hoffmann, M. Wilmanns, R. Lang, et al. Cellular Target Genes of Epstein-Barr Virus Nuclear Antigen 2 J. Virol., October 1, 2006; 80(19): 9761 - 9771. [Abstract] [Full Text] [PDF]