Secreted CEACAM1 Splice Variants in Rat Cell Lines and in Vivo in Rat Serum

Budt, Matthias; Michely, Beate; Mm, Müller; Reutter, Werner; Lucka, Lothar

doi:10.1006/bbrc.2002.6704

Cited by 17 publications

(14 citation statements)

References 36 publications

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“…The generation, expression, and purification of the His-tagged cytoplasmic domain of rat CEACAM1-L (aa 447-519, CC1-L-cyto-His, 14 kDa) and the His-tagged control protein resulting from a frameshift of the UDP-N-acetylglucosamine-2-epimerase/Nacetylmannosamine kinase cDNA (GNE, 12 kDa, Fig. 2A) was done as described (40). The purified His-tagged cytoplasmic domain of the ␣3 integrin subunit was kindly provided by Diana Mutz (Berlin, Germany).…”

Section: Methodsmentioning

confidence: 99%

The Cell Adhesion Receptor Carcinoembryonic Antigen-related Cell Adhesion Molecule 1 Regulates Nucleocytoplasmic Trafficking of DNA Polymerase δ-Interacting Protein 38

Klaile

Kannicht³

et al. 2007

Journal of Biological Chemistry

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The homophilic cell-cell adhesion receptor CEACAM1 (carcinoembryonic antigen-related cell adhesion molecule 1, CD66a) acts as a regulator of contact-dependent cell survival, differentiation, and growth. It is involved in the control of proliferation in hematopoietic and epithelial cells and can act as a tumor suppressor. In this study, we identify DNA polymerase ␦-interacting protein 38 (PDIP38) as a novel binding partner for CEACAM1-L and CEACAM1-S. We show that PDIP38 can occur in the nucleus, in the cytoplasm and at the plasma membrane in NBT-II, IEC18, RBE, and HeLa cells and that the distribution in NBT-II cells is influenced by the confluency of the cells. We also demonstrate that the interaction of CEACAM1 and PDIP38 is of functional importance in NBT-II cells, which co-express the long and the short CEACAM1 isoform. In subconfluent, proliferating NBT-II cells, perturbation of CEACAM1 by antibody clustering induces increased binding to PDIP38 and results in rapid recruitment of PDIP38 to the plasma membrane. The same treatment of confluent, quiescent NBT-II cells leads to a different response, i.e. translocation of PDIP38 to the nucleus. Together, our data show that PDIP38 can shuttle between the cytoplasmic and the nuclear compartments and that its subcellular localization is regulated by CEACAM1, implicating that PDIP38 may constitute a novel downstream target of CEACAM1 signaling.The fate of a cell is controlled by its environment, including the extracellular matrix, neighboring cells, and soluble factors. The signals mediated by this environment frequently are transduced by components of cell-matrix or cell-cell adhesion complexes, like integrins, Ig-cell adhesion molecules, or cadherins (1). CEACAM1 3 (carcinoembryonic antigen-related cell adhesion molecule 1) is a cell-cell adhesion receptor belonging to the CEA family within the Ig-like cell adhesion molecules. CEACAM1 acts as an important regulator of contactdependent control of cell survival, differentiation, and growth in various normal and transformed/cancerous cells of epithelial, endothelial, and hematopoietic origin, as reviewed previously (2, 3).The two major CEACAM1 isoforms are co-expressed in most cells and consist of four extracellular Ig-like domains, a transmembrane domain, and, as a result of differential splicing, a long (L, 71 aa) or a short (S, 10 aa) cytoplasmic domain. Both isoforms mediate cell-cell adhesion via homophilic binding (4, 5). CEACAM1 can also bind to other CEA family members (6) and is used as a receptor by viral and bacterial pathogens (7-9). Recent studies show that there is an important role for CEACAM1 in modulating the immune responses associated with infection, inflammation, and cancer, as reviewed previously (10, 11). CEACAM1 controls differentiation processes (12-14) and apoptosis (13,(15)(16)(17) and can act as a tumor suppressor, as reviewed before (2, 18). We have previously demonstrated that CEACAM1 is implicated in the regulation of proliferation and contact inhibition in epithelial NBT-II cells (19, *...

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Section: Methodsmentioning

confidence: 99%

The Cell Adhesion Receptor Carcinoembryonic Antigen-related Cell Adhesion Molecule 1 Regulates Nucleocytoplasmic Trafficking of DNA Polymerase δ-Interacting Protein 38

Klaile

Kannicht³

et al. 2007

Journal of Biological Chemistry

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“…The mouse mAb Be9.2, the rabbit pAb aCC16, and the rabbit anti-CEACAM1-L-cyto antiserum were described previously [8,28,29]. Antibodies were purified on fast-flow protein GSepharose (Amersham Biosciences, Freiburg, Germany).…”

Section: Antibodies and Reagentsmentioning

confidence: 99%

CEACAM1 (CD66a) mediates delay of spontaneous and Fas ligand-induced apoptosis in granulocytes

et al. 2005

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Granulocytes form the first and fastest line of defense against pathogenic infections. Their survival is limited by apoptosis, a process that is critical for the resolution of inflammation. Pro-apoptotic and pro-inflammatory cytokines, as well as several receptors, can alter the lifespan of granulocytes. Here we report that the carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1, CD66a) is involved in the regulation of granulocyte survival. Until now CEACAM1 is described to control cell proliferation, cell migration, tumor growth, angiogenesis and diverse leukocyte functions. However, very little is known about its role in granulocytes. We found that CEACAM1 expression in resting rat granulocytes is significantly higher than in other leukocyte subtypes. Stimulation led to a strongly increased CEACAM1 cell surface expression and to release of soluble CEACAM1. DNA fragmentation assays and annexin V staining revealed that binding of CEACAM1-specific antibodies, Fab fragments and soluble CEACAM1-Fc constructs to cell surface-expressed CEACAM1 causes a delay of spontaneous and Fas ligand (CD95L)-induced apoptosis. Tyrosine phosphorylation of CEACAM1-L, its association with SHP-1, the activation of Erk1/2 and caspase-3 appeared to be crucial for the CEACAM1-mediated anti-apoptotic effect. These findings provide evidence that CEACAM1 influences the resolution of inflammation by prolonging the survival of rat granulocytes.

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“…The cytoplasmic domain of rat CEACAM1-L (aa 447-519, CC1-cyto) (Budt et al, 2002) was cloned into the BamHI/PstI sites of pGBKT7. Yeast strain AH109 was sequentially transformed with pGBKT7-CC1-cyto and the rat liver MATCHMAKER cDNA library.…”

Section: Yeast Two-hybrid Analysismentioning

confidence: 99%

“…and GST (26 kDa) were expressed in E. coli BL21-star (Invitrogen, Karlsruhe, Germany) and purified using glutathione-Sepharose (Amersham Biosciences, Uppsala, Sweden). The generation, expression and purification of the His-tagged cytoplasmic domain of rat CEACAM1-L (aa 447-519, CC1-cyto-His) was done as described (Budt et al, 2002). The purified His-tagged cytoplasmic domain of the ␣3 integrin subunit was kindly provided by Diana Mutz (Berlin, Germany)…”

Section: Generation and Purification Of Recombinant Proteinsmentioning

confidence: 99%

CEACAM1 functionally interacts with filamin A and exerts a dual role in the regulation of cell migration

Klaile

Kannicht³

et al. 2005

Journal of Cell Science

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The carcinoembryonic antigen-related cell adhesion molecule CEACAM1 (CD66a) and the scaffolding protein filamin A have both been implicated in tumor cell migration. In the present study we identified filamin A as a novel binding partner for the CEACAM1-L cytoplasmic domain in a yeast two-hybrid screen. Direct binding was shown by surface plasmon resonance analysis and by affinity precipitation assays. The association was shown for human and rodent CEACAM1-L in endogenous CEACAM1-L expressing cells. To address functional aspects of the interaction, we used a well-established melanoma cell system. We found in different migration studies that the interaction of CEACAM1-L and filamin A drastically reduced migration and cell scattering, whereas each of these proteins when expressed alone, acted promigratory. CEACAM1-L binding to filamin A reduced the interaction of the latter with RalA, a member of the Ras-family of GTPases. Furthermore, co-expression of CEACAM1-L and filamin A led to a reduced focal adhesion turnover. Independent of the presence of filamin A, the expression of CEACAM1-L led to an increased phosphorylation of focal adhesions and to altered cytoskeletal rearrangements during monolayer wound healing assays. Together, our data demonstrate a novel mechanism for how CEACAM1-L regulates cell migration via its interaction with filamin A.

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Secreted CEACAM1 Splice Variants in Rat Cell Lines and in Vivo in Rat Serum

Cited by 17 publications

References 36 publications

The Cell Adhesion Receptor Carcinoembryonic Antigen-related Cell Adhesion Molecule 1 Regulates Nucleocytoplasmic Trafficking of DNA Polymerase δ-Interacting Protein 38

The Cell Adhesion Receptor Carcinoembryonic Antigen-related Cell Adhesion Molecule 1 Regulates Nucleocytoplasmic Trafficking of DNA Polymerase δ-Interacting Protein 38

CEACAM1 (CD66a) mediates delay of spontaneous and Fas ligand-induced apoptosis in granulocytes

CEACAM1 functionally interacts with filamin A and exerts a dual role in the regulation of cell migration

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