| 1. |
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| 2. |
- Lindahl, E, et al.
(author)
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Cellular internalization of proinsulin C-peptide
- 2007
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In: Cellular and molecular life sciences : CMLS. - : Springer Science and Business Media LLC. - 1420-682X .- 1420-9071. ; 64:4, s. 479-486
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Journal article (peer-reviewed)
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| 13. |
- Hunter, I, et al.
(author)
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Evidence for regulated dimerization of cell-cell adhesion molecule (C-CAM) in epithelial cells
- 1996
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In: The Biochemical journal. - : Portland Press Ltd.. - 0264-6021 .- 1470-8728. ; 320320 ( Pt 3), s. 847-853
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Journal article (peer-reviewed)abstract
- C-CAM is a Ca2+-independent cell adhesion molecule (CAM) belonging to the immunoglobulin superfamily. Addition of chemical cross-linkers to isolated rat liver plasma membranes, intact epithelial cells and purified preparations of C-CAM stabilized one major C-CAM-containing product whose apparent molecular mass was approximately twice that of the C-CAM monomer. The failure to detect additional proteins after cleavage of the cross-linked species demonstrated that C-CAM exists as non-covalently linked dimers both in solution and on the cell surface. Dimerization occurred to the same extent in adherent monolayers and in single cell populations, indicating that dimer formation was the result of cis- interactions within the membranes of individual cells. Using isoform-specific anti-peptide antibodies, both C-CAM1 and C-CAM2 were found to be involved in dimerization, forming predominantly homo-dimeric species. Both calmodulin and Ca2+ ionophore modulated the level of dimer formation, suggesting a role for regulated self-association in the functional activity of C-CAM.
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| 17. |
- Klaile, E, et al.
(author)
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The CEACAM1 N-terminal Ig domain mediates cis- and trans-binding and is essential for allosteric rearrangements of CEACAM1 microclusters
- 2009
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In: The Journal of cell biology. - : Rockefeller University Press. - 1540-8140 .- 0021-9525. ; 187:4, s. 553-567
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Journal article (peer-reviewed)abstract
- Cell adhesion molecules (CAMs) sense the extracellular microenvironment and transmit signals to the intracellular compartment. In this investigation, we addressed the mechanism of signal generation by ectodomains of single-pass transmembrane homophilic CAMs. We analyzed the structure and homophilic interactions of carcinoembryonic antigen (CEA)–related CAM 1 (CEACAM1), which regulates cell proliferation, apoptosis, motility, morphogenesis, and microbial responses. Soluble and membrane-attached CEACAM1 ectodomains were investigated by surface plasmon resonance–based biosensor analysis, molecular electron tomography, and chemical cross-linking. The CEACAM1 ectodomain, which is composed of four glycosylated immunoglobulin-like (Ig) domains, is highly flexible and participates in both antiparallel (trans) and parallel (cis) homophilic binding. Membrane-attached CEACAM1 ectodomains form microclusters in which all four Ig domains participate. Trans-binding between the N-terminal Ig domains increases formation of CEACAM1 cis-dimers and changes CEACAM1 interactions within the microclusters. These data suggest that CEACAM1 transmembrane signaling is initiated by adhesion-regulated changes of cis-interactions that are transmitted to the inner phase of the plasma membrane.
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| 20. |
- Muller, MM, et al.
(author)
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Homophilic adhesion and CEACAM1-S regulate dimerization of CEACAM1-L and recruitment of SHP-2 and c-Src
- 2009
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In: The Journal of cell biology. - : Rockefeller University Press. - 1540-8140 .- 0021-9525. ; 187:4, s. 569-581
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Journal article (peer-reviewed)abstract
- Carcinoembryonic antigen (CEA)–related cell adhesion molecule 1 (CAM1 [CEACAM1]) mediates homophilic cell adhesion and regulates signaling. Although there is evidence that CEACAM1 binds and activates SHP-1, SHP-2, and c-Src, knowledge about the mechanism of transmembrane signaling is lacking. To analyze the regulation of SHP-1/SHP-2/c-Src binding, we expressed various CFP/YFP-tagged CEACAM1 isoforms in epithelial cells. The supramolecular organization of CEACAM1 was examined by cross-linking, coclustering, coimmunoprecipitation, and fluorescence resonance energy transfer. SHP-1/SHP-2/c-Src binding was monitored by coimmunoprecipitation and phosphotyrosine-induced recruitment to CEACAM1-L in cellular monolayers. We find that trans-homophilic CEACAM1 binding induces cis-dimerization by an allosteric mechanism transmitted by the N-terminal immunoglobulin-like domain. The balance of SHP-2 and c-Src binding is dependent on the monomer/dimer equilibrium of CEACAM1-L and is regulated by trans-binding, whereas SHP-1 does not bind under physiological conditions. CEACAM1-L homodimer formation is reduced by coexpression of CEACAM1-S and modulated by antibody ligation. These data suggest that transmembrane signaling by CEACAM1 operates by alteration of the monomer/dimer equilibrium, which leads to changes in the SHP-2/c-Src–binding ratio.
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| 21. |
- Muller, MM, et al.
(author)
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Transmembrane CEACAM1 affects integrin-dependent signaling and regulates extracellular matrix protein-specific morphology and migration of endothelial cells
- 2005
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In: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 105:10, s. 3925-3934
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Journal article (peer-reviewed)abstract
- 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.
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| 24. |
- Obrink, B
(author)
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Is CEACAM1 a lymphangiogenic switch?
- 2007
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In: BLOOD. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 110:13, s. 4137-4138
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Journal article (other academic/artistic)abstract
- Newly formed lymphatic capillaries closely associated with malignant tumors have a key role in metastasis, but much remains to be learned about the trigger and mechanisms of lymphangiogenesis. In this issue of Blood, Kilic and colleagues report that CEACAM1, recognized as a possible lymphangiogenic switch, is expressed in newly formed tumor-associated lymphatic capillaries, and that it can trigger reprogramming of microvascular endothelial cells to lymphatic endothelial cells.
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| 25. |
- Obrink, B
(author)
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On the role of CEACAM1 in cancer
- 2008
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In: Lung cancer (Amsterdam, Netherlands). - : Elsevier BV. - 0169-5002. ; 60:3, s. 309-312
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Journal article (other academic/artistic)
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| 28. |
- Ruoslahti, E, et al.
(author)
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Common principles in cell adhesion
- 1996
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In: Experimental cell research. - : Elsevier BV. - 0014-4827. ; 227:1, s. 1-11
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Journal article (peer-reviewed)
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| 29. |
- Sawa, H, et al.
(author)
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Spatiotemporal expression of C-CAM in the rat placenta
- 1997
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In: The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society. - : SAGE Publications. - 0022-1554. ; 45:7, s. 1021-1034
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Journal article (peer-reviewed)abstract
- We investigated the expression of the immunoglobulin superfamily cell adhesion molecule, C-CAM, in developing and mature rat placenta. By immunohistochemical staining at the light microscopic level, no C-CAM-expression was seen before Day 9 of gestation, when it appeared in the trophoblasts of ectoplacental cones. On Day 10.5, spongiotrophoblasts and invasive trophoblasts around the maternal vessels of the decidua basalis were stained positively. On Day 12.5, C-CAM was detected in the spongiotrophoblasts of the junctional layer, but labyrinth trophoblasts and secondary giant trophoblasts were not stained. On Day 17.5, C-CAM was found only in the labyrinth and lacunae of the junctional layer. At this stage, both the labyrinth cytotrophoblasts of the maternal blood vessels and the endothelial cells of the embryonic capillaries were strongly stained. Placental tissues from gestational Days 12.5 and 17.5 were analyzed by immunoelectron microscopy to determine the location of C-CAM at the subcellular level. On Day 12.5, positive staining of the spongiotrophoblasts was observed, mainly on surface membranes and microvilli between loosely associated cells. On Day 17.5, staining was found primarily on the microvilli of the maternal luminal surfaces of the labyrinth cytotrophoblasts, and both on the luminal surface and in the cytoplasm of endothelial cells of the embryonic vessels. RT-PCR analysis and Southern blotting of the PCR products revealed expression of mRNA species for both of the major isoforms, C-CAM1 and C-CAM2. Immunoblotting analysis of C-CAM isolated from 12.5-day and 14.5-day placentae showed that it appeared as a broad band with an apparent molecular mass of 110–170 kD. In summary, C-CAM was strongly expressed in a specific spatiotemporal pattern in trophoblasts actively involved in formation of the placental tissue, suggesting an important role in placental development. In the mature placenta, C-CAM expression was confined to the trophoblastic and endothelial cells lining the maternal and embryonic vessels, respectively, suggesting important functions in placental physiology.
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| 34. |
- Sundberg, U, et al.
(author)
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CEACAM1 isoforms with different cytoplasmic domains show different localization, organization and adhesive properties in polarized epithelial cells
- 2002
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In: Journal of cell science. - : The Company of Biologists. - 0021-9533 .- 1477-9137. ; 115:6Pt 6, s. 1273-1284
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Journal article (peer-reviewed)abstract
- CEACAM1 is a signaling cell adhesion molecule expressed in epithelia,vessel endothelia and leukocytes. It is expressed as two major isoforms with different cytoplasmic domains. CEACAM1 occurs both in cell-cell contact areas and on apical surfaces of polarized epithelial cells, but it is not known how the different isoforms are distributed in polarized cells or what the functions of CEACAM1 are in the apical surfaces. We investigated the localization and organization of the two CEACAM1 isoforms in transfected,polarized MDCK cells by confocal microscopy and differential surface labelling. CEACAM1-L was found on both the apical and the lateral surfaces,whereas CEACAM1-S appeared exclusively on the apical surfaces. Maintenance of the lateral localization of CEACAM1-L required homophilic binding between CEACAM1-L molecules on adjacent cells. Double-labelling with anti-CEACAM1 antibodies directed against different epitopes indicated that apical CEACAM1-L occurred either in a homophilic adhesive state or in a free non-adhesive state. CEACAM1-S appeared almost exclusively in the homophilic adhesive state. These findings suggest that CEACAM1 mediates adhesive bonds between adjacent microvilli on the apical surfaces.
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| 35. |
- Sundberg, U, et al.
(author)
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The cytoplasmic domain of CEACAM1-L controls its lateral localization and the organization of desmosomes in polarized epithelial cells
- 2004
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In: Journal of cell science. - : The Company of Biologists. - 0021-9533 .- 1477-9137. ; 117:7Pt 7, s. 1091-1104
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Journal article (peer-reviewed)abstract
- Two CEACAM1 isoforms with different cytoplasmic domains, CEACAM1-L and CEACAM1-S, are unequally distributed in polarized epithelial MDCK cells. CEACAM1-S is exclusively apical whereas CEACAM1-L occurs both in apical and lateral cell surfaces. Using confocal microscopy and CEACAM1-L mutants, we identified several amino acids in the cytoplasmic domain that were instrumental for the lateral localization. Tyr515, but not Tyr488, constituted a prominent lateral targeting signal. Pervanadate-stimulated Tyr phosphorylation induced rapid phosphatidylinositol 3-kinase-dependent disappearance of lateral CEACAM1-L, whereas staurosporine, a Ser/Thr kinase inhibitor, resulted in slower phosphatidylinositol 3-kinase-independent disappearance. Both drugs caused accumulation of CEACAM1-L in a late endosome/lysosome compartment. Colocalization studies of occludin, ZO-1, E-cadherin, β-catenin and desmoplakin indicated that laterally localized CEACAM1-L was present in adherens junctions but not in tight junctions or desmosomes. Overexpressed CEACAM1-L did not affect the organization of tight junction or adherens junction proteins, but perturbed the arrangement of desmosomes. The abundance of desmosomes in the lateral cell surfaces decreased significantly and the submembraneous cytokeratin filaments became disorganized. The signal for desmosomal perturbance resided within amino acids 484-518 in the C-terminal part of the cytoplasmic domain, among which an intact Tyr515 was indispensable.
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