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

J. Biol. Chem., Vol. 279, Issue 30, 31149-31156, July 23, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/30/31149    most recent M403587200v1 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 Heiz, M. Articles by Novak-Hofer, I. Search for Related Content PubMed PubMed Citation Articles by Heiz, M. Articles by Novak-Hofer, I. Social Bookmarking                      What's this?

Hepatocyte Growth Factor-induced Ectodomain Shedding of Cell Adhesion Molecule L1

ROLE OF THE L1 CYTOPLASMIC DOMAIN^*

Monika Heiz, Jürgen Grünberg, P. August Schubiger, and Ilse Novak-Hofer

From the Center for Radiopharmaceutical Science ETH-PSI-USZ; Paul Scherrer Institute, CH-5232 Villigen, Switzerland

The L1 cell adhesion molecule and its soluble form are tumor-associated proteins and potential markers for tumor staging as well as targets for therapeutic intervention. Soluble L1 is produced by metalloprotease-mediated ectodomain shedding of L1. We investigated effects of hepatocyte growth factor (HGF), a growth factor shown to increase invasiveness of renal carcinoma cells, on ectodomain shedding of L1 from these cells. All of the tested L1-positive renal carcinoma cell lines released a 180-kDa form of L1 into the medium. In the presence of serum, addition of HGF led to a dose-dependent increase in L1 shedding with a maximum reached at 5 ng/ml. In contrast, L1 shedding was inhibited by glial cell line-derived neurotrophic factor (GDNF). The tyrosine kinase inhibitor Genistein reduced basal and HGF-stimulated L1 shedding, indicating that protein phosphorylation is involved. To investigate the role of the L1 intracellular domain, two mutants of the L1 cytoplasmic part were constructed. L1trun lacking the complete intracellular domain showed enhanced basal shedding. In a L1YH mutant, containing the mutation tyrosine 1229 to histidine that deletes the ankyrin binding motif of L1, basal shedding was reduced. Disruption of actin assembly by cytochalasin D also reduced shedding of L1. These results indicate that the cytoplasmic domain regulates basal shedding of L1, and association with the cytoskeleton through the L1 ankyrin binding site is involved. HGF stimulated L1 shedding in both mutants, indicating that receptor-mediated phosphorylation in the L1 cytoplasmic domain is not required for HGF-stimulated shedding.

Received for publication, March 31, 2004 , and in revised form, May 18, 2004.

^* This work was supported by Swiss National Science Foundation Grant 3100A0-100200. 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: Center for Radiopharmaceutical Science ETH-PSI-USZ, Paul Scherrer Institute, CH-5232 Villigen, Switzerland. Tel.: 41-56-310-4067; Fax: 41-56-310-2849; E-mail: ilse.novak{at}psi.ch.

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

This article has been cited by other articles:

				K. Hayashida, P. D. Stahl, and P. W. Park Syndecan-1 Ectodomain Shedding Is Regulated by the Small GTPase Rab5 J. Biol. Chem., December 19, 2008; 283(51): 35435 - 35444. [Abstract] [Full Text] [PDF]

				K. Knogler, J. Grunberg, K. Zimmermann, S. Cohrs, M. Honer, S. Ametamey, P. Altevogt, M. Fogel, P. A. Schubiger, and I. Novak-Hofer Copper-67 Radioimmunotherapy and Growth Inhibition by Anti-L1-Cell Adhesion Molecule Monoclonal Antibodies in a Therapy Model of Ovarian Cancer Metastasis Clin. Cancer Res., January 15, 2007; 13(2): 603 - 611. [Abstract] [Full Text] [PDF]

				M. Shtutman, E. Levina, P. Ohouo, M. Baig, and I. B. Roninson Cell Adhesion Molecule L1 Disrupts E-Cadherin-Containing Adherens Junctions and Increases Scattering and Motility of MCF7 Breast Carcinoma Cells Cancer Res., December 1, 2006; 66(23): 11370 - 11380. [Abstract] [Full Text] [PDF]

				T. Maretzky, M. Schulte, A. Ludwig, S. Rose-John, C. Blobel, D. Hartmann, P. Altevogt, P. Saftig, and K. Reiss L1 Is Sequentially Processed by Two Differently Activated Metalloproteases and Presenilin/{gamma}-Secretase and Regulates Neural Cell Adhesion, Cell Migration, and Neurite Outgrowth Mol. Cell. Biol., October 15, 2005; 25(20): 9040 - 9053. [Abstract] [Full Text] [PDF]

				P. Gutwein, A. Stoeck, S. Riedle, D. Gast, S. Runz, T. P. Condon, A. Marme, M.-C. Phong, O. Linderkamp, A. Skorokhod, et al. Cleavage of L1 in Exosomes and Apoptotic Membrane Vesicles Released from Ovarian Carcinoma Cells Clin. Cancer Res., April 1, 2005; 11(7): 2492 - 2501. [Abstract] [Full Text] [PDF]