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Blood, 15 May 2005, Vol. 105, No. 10, pp. 3925-3934. Prepublished online as a Blood First Edition Paper on February 1, 2005; DOI 10.1182/blood-2004-09-3618. This Article Full Text Full Text (PDF) Erratum (v106,p407) All Versions of this Article: 2004-09-3618v1 105/10/3925    most recent Alert me when this article is cited 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 Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Müller, M. M. Articles by Lucka, L. Search for Related Content PubMed PubMed Citation Articles by Müller, M. M. Articles by Lucka, L. Related Collections Hemostasis, Thrombosis, and Vascular Biology Cell Adhesion and Motility Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Transmembrane CEACAM1 affects integrin-dependent signaling and regulates extracellular matrix protein–specific morphology and migration of endothelial cells Mario M. Müller, Bernhard B. Singer, Esther Klaile, Björn Öbrink, and Lothar Lucka From the Institut für Biochemie und Molekularbiologie, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin-Dahlem, Germany; and the Department of Cell and Molecular Biology, Medical Nobel Institute, Karolinska Institutet, Stockholm, Sweden. Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1/CD66a), expressed on leukocytes, epithelia, and endothelia mediates homophilic cell adhesion. It plays an important role in cell morphogenesis and, recently, soluble CEACAM1 isoforms have been implicated in angiogenesis. In the present study, we investigated the function of long transmembrane isoform of CEACAM1 (CEACAM1-L) in cultured rat brain endothelial cells. We observed that expression of CEACAM1-L promotes network formation on basement membrane Matrigel and increased cell motility after monolayer injury. During cell-matrix adhesion, CEACAM1-L translocated into the Triton X-100–insoluble cytoskeletal fraction and affected cell spreading and cell morphology on Matrigel and laminin-1 but not on fibronectin. On laminin-1, CEACAM1-L–expressing cells developed protrusions with lamellipodia, showed less stress fiber formation, reduced focal adhesion kinase (FAK) tyrosine phosphorylation, and decreased focal adhesion formation leading to high motility. CEACAM1-L–mediated morphologic alterations were sensitive to RhoA activation via lysophosphatidic acid (LPA) treatment and dependent on Rac1 activation. Furthermore, we demonstrate a matrix protein–dependent association of CEACAM1-L with talin, an important regulator of integrin function. Taken together, our results suggest that transmembrane CEACAM1-L expressed on endothelial cells is implicated in the activation phase of angiogenesis by affecting the cytoskeleton architecture and integrin-mediated signaling. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: E. Klaile, O. Vorontsova, K. Sigmundsson, M. M. Muller, B. B. Singer, L.-G. Ofverstedt, S. Svensson, U. Skoglund, and B. Obrink The CEACAM1 N-terminal Ig domain mediates cis- and trans-binding and is essential for allosteric rearrangements of CEACAM1 microclusters J. Cell Biol., November 16, 2009; 187(4): 553 - 567. [Abstract] [Full Text] [PDF] M. M. Muller, E. Klaile, O. Vorontsova, B. B. Singer, and B. Obrink Homophilic adhesion and CEACAM1-S regulate dimerization of CEACAM1-L and recruitment of SHP-2 and c-Src J. Cell Biol., November 16, 2009; 187(4): 569 - 581. [Abstract] [Full Text] [PDF] L. Jin, Y. Li, C.-J. Chen, M. A. Sherman, K. Le, and J. E. Shively Direct Interaction of Tumor Suppressor CEACAM1 with Beta Catenin: Identification of Key Residues in the Long Cytoplasmic Domain Experimental Biology and Medicine, July 1, 2008; 233(7): 849 - 859. [Abstract] [Full Text] [PDF] E. Klaile, M. M. Muller, C. Kannicht, W. Otto, B. B. Singer, W. Reutter, B. Obrink, and L. Lucka The Cell Adhesion Receptor Carcinoembryonic Antigen-related Cell Adhesion Molecule 1 Regulates Nucleocytoplasmic Trafficking of DNA Polymerase {delta}-Interacting Protein 38 J. Biol. Chem., September 7, 2007; 282(36): 26629 - 26640. [Abstract] [Full Text] [PDF] T. Schmitter, S. Pils, S. Weibel, F. Agerer, L. Peterson, A. Buntru, K. Kopp, and C. R. Hauck Opa Proteins of Pathogenic Neisseriae Initiate Src Kinase-Dependent or Lipid Raft-Mediated Uptake via Distinct Human Carcinoembryonic Antigen-Related Cell Adhesion Molecule Isoforms Infect. Immun., August 1, 2007; 75(8): 4116 - 4126. [Abstract] [Full Text] [PDF] A.-M. Bamberger, J. Briese, J. Gotze, I. Erdmann, H. M. Schulte, C. Wagener, and P. Nollau Stimulation of CEACAM1 expression by 12-O-tetradecanoylphorbol-13-acetate (TPA) and calcium ionophore A23187 in endometrial carcinoma cells Carcinogenesis, March 1, 2006; 27(3): 483 - 490. [Abstract] [Full Text] [PDF] A.-M. Bamberger, V. Minas, S. N. Kalantaridou, J. Radde, H. Sadeghian, T. Loning, I. Charalampopoulos, J. Brummer, C. Wagener, C. M. Bamberger, et al. Corticotropin-Releasing Hormone Modulates Human Trophoblast Invasion through Carcinoembryonic Antigen-Related Cell Adhesion Molecule-1 Regulation Am. J. Pathol., January 1, 2006; 168(1): 141 - 150. [Abstract] [Full Text] [PDF] E. Klaile, M. M. Muller, C. Kannicht, B. B. Singer, and L. Lucka CEACAM1 functionally interacts with filamin A and exerts a dual role in the regulation of cell migration J. Cell Sci., December 1, 2005; 118(23): 5513 - 5524. [Abstract] [Full Text] [PDF]

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