Plays a central role in tight junction maintenance via the complex formed with ARHGAP17, which acts by regulating the uptake of polarity proteins at tight junctions. Appears to regulate endothelial cell migration and tube formation. May also play a role in the assembly of endothelial cell-cell junctions.
J. Cell Biol. 152, 1247-1254 (2001)[PubMed:11257124]
Angiostatin, a circulating inhibitor of angiogenesis, was identified by its ability to maintain dormancy of established metastases in vivo. In vitro, angiostatin inhibits endothelial cell migration, proliferation, and tube formation, and induces apoptosis in a cell type-specific manner. We have used a construct encoding the kringle domains 1--4 of angiostatin to screen a placenta yeast two-hybrid cDNA library for angiostatin-binding peptides. Here we report the identification of angiomotin, a novel protein that mediates angiostatin inhibition of migration and tube formation of endothelial cells. In vivo, angiomotin is expressed in the endothelial cells of capillaries as well as larger vessels of the human placenta. Upon expression of angiomotin in HeLa cells, angiomotin bound and internalized fluorescein-labeled angiostatin. Transfected angiomotin as well as endogenous angiomotin protein were localized to the leading edge of migrating endothelial cells. Expression of angiomotin in endothelial cells resulted in increased cell migration, suggesting a stimulatory role of angiomotin in cell motility. However, treatment with angiostatin inhibited migration and tube formation in angiomotin-expressing cells but not in control cells. These findings indicate that angiostatin inhibits cell migration by interfering with angiomotin activity in endothelial cells.
Using functional and proteomic screens of proteins that regulate the Cdc42 GTPase, we have identified a network of protein interactions that center around the Cdc42 RhoGAP Rich1 and organize apical polarity in MDCK epithelial cells. Rich1 binds the scaffolding protein angiomotin (Amot) and is thereby targeted to a protein complex at tight junctions (TJs) containing the PDZ-domain proteins Pals1, Patj, and Par-3. Regulation of Cdc42 by Rich1 is necessary for maintenance of TJs, and Rich1 is therefore an important mediator of this polarity complex. Furthermore, the coiled-coil domain of Amot, with which it binds Rich1, is necessary for localization to apical membranes and is required for Amot to relocalize Pals1 and Par-3 to internal puncta. We propose that Rich1 and Amot maintain TJ integrity by the coordinate regulation of Cdc42 and by linking specific components of the TJ to intracellular protein trafficking.
Interacting selectively and non-covalently with angiostatin, a proteolytic product of plasminogen or plasmin containing at least one intact kringle domain, and which is an inhibitor of angiogenesis.
J. Cell Biol. 152, 1247-1254 (2001)[PubMed:11257124]
Angiostatin, a circulating inhibitor of angiogenesis, was identified by its ability to maintain dormancy of established metastases in vivo. In vitro, angiostatin inhibits endothelial cell migration, proliferation, and tube formation, and induces apoptosis in a cell type-specific manner. We have used a construct encoding the kringle domains 1--4 of angiostatin to screen a placenta yeast two-hybrid cDNA library for angiostatin-binding peptides. Here we report the identification of angiomotin, a novel protein that mediates angiostatin inhibition of migration and tube formation of endothelial cells. In vivo, angiomotin is expressed in the endothelial cells of capillaries as well as larger vessels of the human placenta. Upon expression of angiomotin in HeLa cells, angiomotin bound and internalized fluorescein-labeled angiostatin. Transfected angiomotin as well as endogenous angiomotin protein were localized to the leading edge of migrating endothelial cells. Expression of angiomotin in endothelial cells resulted in increased cell migration, suggesting a stimulatory role of angiomotin in cell motility. However, treatment with angiostatin inhibited migration and tube formation in angiomotin-expressing cells but not in control cells. These findings indicate that angiostatin inhibits cell migration by interfering with angiomotin activity in endothelial cells.
Evidence
2:
Inferred from Direct AssayUniProtKB
Evidence for Iso 2
We have previously identified angiomotin by its ability to bind to and mediate the anti-angiogenic properties of angiostatin. In vivo and in vitro data indicate an essential role of angiomotin in endothelial cell motility. Here we show that angiostatin binds angiomotin on the cell surface and provide evidence for a transmembrane model for the topology of both p80 and p130 angiomotin isoforms. Immunofluorescence analysis shows that angiomotin co-localized with ZO-1 in cell-cell contacts in endothelial cells in vitro and in angiogenic blood vessels of the postnatal mouse retina in vivo. Transfection of p80 as well as p130 angiomotin in Chinese hamster ovary cells resulted in junctional localization of both isoforms. Furthermore, p130 angiomotin could recruit ZO-1 to actin stress fibers. The p130 but not p80 isoform could be coprecipitated with MAGI-1b, a component of endothelial tight junctions. Paracellular permeability, as measured by diffusion of fluorescein isothiocyanate-dextran, was reduced by p80 and p130 angiomotin expression with 70 and 88%, respectively, compared with control. Angiostatin did not have any effect on cell permeability but inhibited the migration of angiomotin-expressing cells in the Boyden chamber assay. We conclude that angiomotin, in addition to controlling cell motility, may play a role in the assembly of endothelial cell-cell junctions.
Interacting selectively and non-covalently with any protein or protein complex (a complex of two or more proteins that may include other nonprotein molecules).
Evidence
1:
Inferred from Physical InteractionHGNC
J. Cell Biol. 152, 1247-1254 (2001)[PubMed:11257124]
Angiostatin, a circulating inhibitor of angiogenesis, was identified by its ability to maintain dormancy of established metastases in vivo. In vitro, angiostatin inhibits endothelial cell migration, proliferation, and tube formation, and induces apoptosis in a cell type-specific manner. We have used a construct encoding the kringle domains 1--4 of angiostatin to screen a placenta yeast two-hybrid cDNA library for angiostatin-binding peptides. Here we report the identification of angiomotin, a novel protein that mediates angiostatin inhibition of migration and tube formation of endothelial cells. In vivo, angiomotin is expressed in the endothelial cells of capillaries as well as larger vessels of the human placenta. Upon expression of angiomotin in HeLa cells, angiomotin bound and internalized fluorescein-labeled angiostatin. Transfected angiomotin as well as endogenous angiomotin protein were localized to the leading edge of migrating endothelial cells. Expression of angiomotin in endothelial cells resulted in increased cell migration, suggesting a stimulatory role of angiomotin in cell motility. However, treatment with angiostatin inhibited migration and tube formation in angiomotin-expressing cells but not in control cells. These findings indicate that angiostatin inhibits cell migration by interfering with angiomotin activity in endothelial cells.
Evidence
2:
Inferred from Physical InteractionIntAct
The Merlin/NF2 tumor suppressor restrains cell growth and tumorigenesis by controlling contact-dependent inhibition of proliferation. We have identified a tight-junction-associated protein complex comprising Merlin, Angiomotin, Patj, and Pals1. We demonstrate that Angiomotin functions downstream of Merlin and upstream of Rich1, a small GTPase Activating Protein, as a positive regulator of Rac1. Merlin, through competitive binding to Angiomotin, releases Rich1 from the Angiomotin-inhibitory complex, allowing Rich1 to inactivate Rac1, ultimately leading to attenuation of Rac1 and Ras-MAPK pathways. Patient-derived Merlin mutants show diminished binding capacities to Angiomotin and are unable to dissociate Rich1 from Angiomotin or inhibit MAPK signaling. Depletion of Angiomotin in Nf2(-/-) Schwann cells attenuates the Ras-MAPK signaling pathway, impedes cellular proliferation in vitro and tumorigenesis in vivo.
Evidence
3:
Inferred from Physical InteractionIntAct
Deubiquitinating enzymes (Dubs) function to remove covalently attached ubiquitin from proteins, thereby controlling substrate activity and/or abundance. For most Dubs, their functions, targets, and regulation are poorly understood. To systematically investigate Dub function, we initiated a global proteomic analysis of Dubs and their associated protein complexes. This was accomplished through the development of a software platform called CompPASS, which uses unbiased metrics to assign confidence measurements to interactions from parallel nonreciprocal proteomic data sets. We identified 774 candidate interacting proteins associated with 75 Dubs. Using Gene Ontology, interactome topology classification, subcellular localization, and functional studies, we link Dubs to diverse processes, including protein turnover, transcription, RNA processing, DNA damage, and endoplasmic reticulum-associated degradation. This work provides the first glimpse into the Dub interaction landscape, places previously unstudied Dubs within putative biological pathways, and identifies previously unknown interactions and protein complexes involved in this increasingly important arm of the ubiquitin-proteasome pathway.
Evidence
4:
Inferred from Physical InteractionUniProtKB
Evidence for Iso 1
In both Drosophila and mammalian systems, the Hippo pathway plays an important role in controlling organ size, mainly through its ability to regulate cell proliferation and apoptosis. The key component in the Hippo pathway is the Yes-associated protein YAP1, which localizes in nucleus, functions as a transcriptional coactivator, and regulates the expression of several proliferation- and apoptosis-related genes. The Hippo pathway negatively regulates YAP1 transcriptional activity by modulating its nuclear-cytoplasmic localization in a phosphorylation-dependent manner. Here, we describe the identification of several new PY motif-containing proteins, including angiomotin-like protein 1 (AMOTL1) and 2 (AMOTL2), as YAP1-associated proteins. We demonstrate that AMOTL1 and AMOTL2 can regulate YAP1 cytoplasm-to-nucleus translocation through direct protein-protein interaction, which can occur independent of YAP1 phosphorylation status. Moreover, down-regulation of AMOTL2 in MCF10A cells promotes epithelial-mesenchymal transition, a phenotype that is also observed in MCF10A cells with YAP1 overexpression. Together, these data support a new mechanism for YAP1 regulation, which is mediated via its direct interactions with angiomotin-like proteins.
Evidence
5:
Inferred from Physical InteractionUniProtKB
Evidence for Iso 1
We have previously identified angiomotin by its ability to bind to and mediate the anti-angiogenic properties of angiostatin. In vivo and in vitro data indicate an essential role of angiomotin in endothelial cell motility. Here we show that angiostatin binds angiomotin on the cell surface and provide evidence for a transmembrane model for the topology of both p80 and p130 angiomotin isoforms. Immunofluorescence analysis shows that angiomotin co-localized with ZO-1 in cell-cell contacts in endothelial cells in vitro and in angiogenic blood vessels of the postnatal mouse retina in vivo. Transfection of p80 as well as p130 angiomotin in Chinese hamster ovary cells resulted in junctional localization of both isoforms. Furthermore, p130 angiomotin could recruit ZO-1 to actin stress fibers. The p130 but not p80 isoform could be coprecipitated with MAGI-1b, a component of endothelial tight junctions. Paracellular permeability, as measured by diffusion of fluorescein isothiocyanate-dextran, was reduced by p80 and p130 angiomotin expression with 70 and 88%, respectively, compared with control. Angiostatin did not have any effect on cell permeability but inhibited the migration of angiomotin-expressing cells in the Boyden chamber assay. We conclude that angiomotin, in addition to controlling cell motility, may play a role in the assembly of endothelial cell-cell junctions.
J. Cell Biol. 152, 1247-1254 (2001)[PubMed:11257124]
Angiostatin, a circulating inhibitor of angiogenesis, was identified by its ability to maintain dormancy of established metastases in vivo. In vitro, angiostatin inhibits endothelial cell migration, proliferation, and tube formation, and induces apoptosis in a cell type-specific manner. We have used a construct encoding the kringle domains 1--4 of angiostatin to screen a placenta yeast two-hybrid cDNA library for angiostatin-binding peptides. Here we report the identification of angiomotin, a novel protein that mediates angiostatin inhibition of migration and tube formation of endothelial cells. In vivo, angiomotin is expressed in the endothelial cells of capillaries as well as larger vessels of the human placenta. Upon expression of angiomotin in HeLa cells, angiomotin bound and internalized fluorescein-labeled angiostatin. Transfected angiomotin as well as endogenous angiomotin protein were localized to the leading edge of migrating endothelial cells. Expression of angiomotin in endothelial cells resulted in increased cell migration, suggesting a stimulatory role of angiomotin in cell motility. However, treatment with angiostatin inhibited migration and tube formation in angiomotin-expressing cells but not in control cells. These findings indicate that angiostatin inhibits cell migration by interfering with angiomotin activity in endothelial cells.
A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly of cytoskeletal structures comprising actin filaments and their associated proteins.
We have previously identified angiomotin by its ability to bind to and mediate the anti-angiogenic properties of angiostatin. In vivo and in vitro data indicate an essential role of angiomotin in endothelial cell motility. Here we show that angiostatin binds angiomotin on the cell surface and provide evidence for a transmembrane model for the topology of both p80 and p130 angiomotin isoforms. Immunofluorescence analysis shows that angiomotin co-localized with ZO-1 in cell-cell contacts in endothelial cells in vitro and in angiogenic blood vessels of the postnatal mouse retina in vivo. Transfection of p80 as well as p130 angiomotin in Chinese hamster ovary cells resulted in junctional localization of both isoforms. Furthermore, p130 angiomotin could recruit ZO-1 to actin stress fibers. The p130 but not p80 isoform could be coprecipitated with MAGI-1b, a component of endothelial tight junctions. Paracellular permeability, as measured by diffusion of fluorescein isothiocyanate-dextran, was reduced by p80 and p130 angiomotin expression with 70 and 88%, respectively, compared with control. Angiostatin did not have any effect on cell permeability but inhibited the migration of angiomotin-expressing cells in the Boyden chamber assay. We conclude that angiomotin, in addition to controlling cell motility, may play a role in the assembly of endothelial cell-cell junctions.
The migration of individual cells within the blastocyst to help establish the multi-layered body plan of the organism (gastrulation). For example, the migration of cells from the surface to the interior of the embryo (ingression).
We have previously identified angiomotin by its ability to bind to and mediate the anti-angiogenic properties of angiostatin. In vivo and in vitro data indicate an essential role of angiomotin in endothelial cell motility. Here we show that angiostatin binds angiomotin on the cell surface and provide evidence for a transmembrane model for the topology of both p80 and p130 angiomotin isoforms. Immunofluorescence analysis shows that angiomotin co-localized with ZO-1 in cell-cell contacts in endothelial cells in vitro and in angiogenic blood vessels of the postnatal mouse retina in vivo. Transfection of p80 as well as p130 angiomotin in Chinese hamster ovary cells resulted in junctional localization of both isoforms. Furthermore, p130 angiomotin could recruit ZO-1 to actin stress fibers. The p130 but not p80 isoform could be coprecipitated with MAGI-1b, a component of endothelial tight junctions. Paracellular permeability, as measured by diffusion of fluorescein isothiocyanate-dextran, was reduced by p80 and p130 angiomotin expression with 70 and 88%, respectively, compared with control. Angiostatin did not have any effect on cell permeability but inhibited the migration of angiomotin-expressing cells in the Boyden chamber assay. We conclude that angiomotin, in addition to controlling cell motility, may play a role in the assembly of endothelial cell-cell junctions.
Any process in which a protein is transported to, and/or maintained in, a specific location at the level of a cell. Localization at the cellular level encompasses movement within the cell, from within the cell to the cell surface, or from one location to another at the surface of a cell.
The Yes-associated protein (YAP) is a transcription coactivator that plays a crucial role in organ size control by promoting cell proliferation and inhibiting apoptosis. The Hippo tumor suppressor pathway inhibits YAP through phosphorylation-induced cytoplasmic retention and degradation. Here we report a novel mechanism of YAP regulation by angiomotin (AMOT) family proteins via a direct interaction. Knockdown of AMOT family protein AMOTL2 in polarized Madin-Darby canine kidney (MDCK) cells leads to YAP activation, as indicated by decreased YAP tight junction localization, attenuated YAP phosphorylation, accumulation of nuclear YAP, and induction of YAP target gene expression. Transcriptional coactivator with PDZ-binding motif (TAZ), the YAP paralog, is also regulated by AMOT in a similar fashion. Furthermore, AMOTL2 knockdown results in loss of cell contact inhibition in a manner dependent on the functions of YAP and TAZ. Our results indicate a potential tumor-suppressing role of AMOT family proteins as components of the Hippo pathway, and demonstrate a novel mechanism of YAP and TAZ inhibition by AMOT-mediated tight junction localization. These observations provide a potential link between the Hippo pathway and cell contact inhibition.
The directed movement of a motile cell or organism, or the directed growth of a cell guided by a specific chemical concentration gradient. Movement may be towards a higher concentration (positive chemotaxis) or towards a lower concentration (negative chemotaxis).
IEAOrtholog Compara
Establishment of cell polarity involved in ameboidal cell migrationdefinition[GO:0003365]‹silver
The specification and formation of anisotropic intracellular organization that contributes to the self-propelled directed movement of an ameboid cell.
The series of molecular signals mediated by the serine/threonine kinase Hippo or one of its orthologs. In Drosophila, Hippo in complex with the scaffold protein Salvador (Sav), phosphorylates and activates Warts (Wts), which in turn phosphorylates and inactivates the Yorkie (Yki) transcriptional activator. The core fly components hippo, sav, wts and mats are conserved in mammals as STK4/3 (MST1/2), SAV1/WW45, LATS1/2 and MOB1.
The Yes-associated protein (YAP) is a transcription coactivator that plays a crucial role in organ size control by promoting cell proliferation and inhibiting apoptosis. The Hippo tumor suppressor pathway inhibits YAP through phosphorylation-induced cytoplasmic retention and degradation. Here we report a novel mechanism of YAP regulation by angiomotin (AMOT) family proteins via a direct interaction. Knockdown of AMOT family protein AMOTL2 in polarized Madin-Darby canine kidney (MDCK) cells leads to YAP activation, as indicated by decreased YAP tight junction localization, attenuated YAP phosphorylation, accumulation of nuclear YAP, and induction of YAP target gene expression. Transcriptional coactivator with PDZ-binding motif (TAZ), the YAP paralog, is also regulated by AMOT in a similar fashion. Furthermore, AMOTL2 knockdown results in loss of cell contact inhibition in a manner dependent on the functions of YAP and TAZ. Our results indicate a potential tumor-suppressing role of AMOT family proteins as components of the Hippo pathway, and demonstrate a novel mechanism of YAP and TAZ inhibition by AMOT-mediated tight junction localization. These observations provide a potential link between the Hippo pathway and cell contact inhibition.
The process whose specific outcome is the progression of the embryo in the uterus over time, from formation of the zygote in the oviduct, to birth. An example of this process is found in Mus musculus.
J. Cell Biol. 152, 1247-1254 (2001)[PubMed:11257124]
Angiostatin, a circulating inhibitor of angiogenesis, was identified by its ability to maintain dormancy of established metastases in vivo. In vitro, angiostatin inhibits endothelial cell migration, proliferation, and tube formation, and induces apoptosis in a cell type-specific manner. We have used a construct encoding the kringle domains 1--4 of angiostatin to screen a placenta yeast two-hybrid cDNA library for angiostatin-binding peptides. Here we report the identification of angiomotin, a novel protein that mediates angiostatin inhibition of migration and tube formation of endothelial cells. In vivo, angiomotin is expressed in the endothelial cells of capillaries as well as larger vessels of the human placenta. Upon expression of angiomotin in HeLa cells, angiomotin bound and internalized fluorescein-labeled angiostatin. Transfected angiomotin as well as endogenous angiomotin protein were localized to the leading edge of migrating endothelial cells. Expression of angiomotin in endothelial cells resulted in increased cell migration, suggesting a stimulatory role of angiomotin in cell motility. However, treatment with angiostatin inhibited migration and tube formation in angiomotin-expressing cells but not in control cells. These findings indicate that angiostatin inhibits cell migration by interfering with angiomotin activity in endothelial cells.
We have previously identified angiomotin by its ability to bind to and mediate the anti-angiogenic properties of angiostatin. In vivo and in vitro data indicate an essential role of angiomotin in endothelial cell motility. Here we show that angiostatin binds angiomotin on the cell surface and provide evidence for a transmembrane model for the topology of both p80 and p130 angiomotin isoforms. Immunofluorescence analysis shows that angiomotin co-localized with ZO-1 in cell-cell contacts in endothelial cells in vitro and in angiogenic blood vessels of the postnatal mouse retina in vivo. Transfection of p80 as well as p130 angiomotin in Chinese hamster ovary cells resulted in junctional localization of both isoforms. Furthermore, p130 angiomotin could recruit ZO-1 to actin stress fibers. The p130 but not p80 isoform could be coprecipitated with MAGI-1b, a component of endothelial tight junctions. Paracellular permeability, as measured by diffusion of fluorescein isothiocyanate-dextran, was reduced by p80 and p130 angiomotin expression with 70 and 88%, respectively, compared with control. Angiostatin did not have any effect on cell permeability but inhibited the migration of angiomotin-expressing cells in the Boyden chamber assay. We conclude that angiomotin, in addition to controlling cell motility, may play a role in the assembly of endothelial cell-cell junctions.
We have previously identified angiomotin by its ability to bind to and mediate the anti-angiogenic properties of angiostatin. In vivo and in vitro data indicate an essential role of angiomotin in endothelial cell motility. Here we show that angiostatin binds angiomotin on the cell surface and provide evidence for a transmembrane model for the topology of both p80 and p130 angiomotin isoforms. Immunofluorescence analysis shows that angiomotin co-localized with ZO-1 in cell-cell contacts in endothelial cells in vitro and in angiogenic blood vessels of the postnatal mouse retina in vivo. Transfection of p80 as well as p130 angiomotin in Chinese hamster ovary cells resulted in junctional localization of both isoforms. Furthermore, p130 angiomotin could recruit ZO-1 to actin stress fibers. The p130 but not p80 isoform could be coprecipitated with MAGI-1b, a component of endothelial tight junctions. Paracellular permeability, as measured by diffusion of fluorescein isothiocyanate-dextran, was reduced by p80 and p130 angiomotin expression with 70 and 88%, respectively, compared with control. Angiostatin did not have any effect on cell permeability but inhibited the migration of angiomotin-expressing cells in the Boyden chamber assay. We conclude that angiomotin, in addition to controlling cell motility, may play a role in the assembly of endothelial cell-cell junctions.
We have previously identified angiomotin by its ability to bind to and mediate the anti-angiogenic properties of angiostatin. In vivo and in vitro data indicate an essential role of angiomotin in endothelial cell motility. Here we show that angiostatin binds angiomotin on the cell surface and provide evidence for a transmembrane model for the topology of both p80 and p130 angiomotin isoforms. Immunofluorescence analysis shows that angiomotin co-localized with ZO-1 in cell-cell contacts in endothelial cells in vitro and in angiogenic blood vessels of the postnatal mouse retina in vivo. Transfection of p80 as well as p130 angiomotin in Chinese hamster ovary cells resulted in junctional localization of both isoforms. Furthermore, p130 angiomotin could recruit ZO-1 to actin stress fibers. The p130 but not p80 isoform could be coprecipitated with MAGI-1b, a component of endothelial tight junctions. Paracellular permeability, as measured by diffusion of fluorescein isothiocyanate-dextran, was reduced by p80 and p130 angiomotin expression with 70 and 88%, respectively, compared with control. Angiostatin did not have any effect on cell permeability but inhibited the migration of angiomotin-expressing cells in the Boyden chamber assay. We conclude that angiomotin, in addition to controlling cell motility, may play a role in the assembly of endothelial cell-cell junctions.
Any process that activates or increases the frequency, rate or extent of the assembly of a stress fiber, a bundle of microfilaments and other proteins found in fibroblasts.
We have previously identified angiomotin by its ability to bind to and mediate the anti-angiogenic properties of angiostatin. In vivo and in vitro data indicate an essential role of angiomotin in endothelial cell motility. Here we show that angiostatin binds angiomotin on the cell surface and provide evidence for a transmembrane model for the topology of both p80 and p130 angiomotin isoforms. Immunofluorescence analysis shows that angiomotin co-localized with ZO-1 in cell-cell contacts in endothelial cells in vitro and in angiogenic blood vessels of the postnatal mouse retina in vivo. Transfection of p80 as well as p130 angiomotin in Chinese hamster ovary cells resulted in junctional localization of both isoforms. Furthermore, p130 angiomotin could recruit ZO-1 to actin stress fibers. The p130 but not p80 isoform could be coprecipitated with MAGI-1b, a component of endothelial tight junctions. Paracellular permeability, as measured by diffusion of fluorescein isothiocyanate-dextran, was reduced by p80 and p130 angiomotin expression with 70 and 88%, respectively, compared with control. Angiostatin did not have any effect on cell permeability but inhibited the migration of angiomotin-expressing cells in the Boyden chamber assay. We conclude that angiomotin, in addition to controlling cell motility, may play a role in the assembly of endothelial cell-cell junctions.
J. Cell Biol. 152, 1247-1254 (2001)[PubMed:11257124]
Angiostatin, a circulating inhibitor of angiogenesis, was identified by its ability to maintain dormancy of established metastases in vivo. In vitro, angiostatin inhibits endothelial cell migration, proliferation, and tube formation, and induces apoptosis in a cell type-specific manner. We have used a construct encoding the kringle domains 1--4 of angiostatin to screen a placenta yeast two-hybrid cDNA library for angiostatin-binding peptides. Here we report the identification of angiomotin, a novel protein that mediates angiostatin inhibition of migration and tube formation of endothelial cells. In vivo, angiomotin is expressed in the endothelial cells of capillaries as well as larger vessels of the human placenta. Upon expression of angiomotin in HeLa cells, angiomotin bound and internalized fluorescein-labeled angiostatin. Transfected angiomotin as well as endogenous angiomotin protein were localized to the leading edge of migrating endothelial cells. Expression of angiomotin in endothelial cells resulted in increased cell migration, suggesting a stimulatory role of angiomotin in cell motility. However, treatment with angiostatin inhibited migration and tube formation in angiomotin-expressing cells but not in control cells. These findings indicate that angiostatin inhibits cell migration by interfering with angiomotin activity in endothelial cells.
A reference proteome is a set of protein sequences derived from a complete proteome which constitutes a defined standard for a particular user community. Reference proteomes are manually defined according to a number of criteria. They cover the proteomes of well- studied model organisms and other proteomes of interest for biomedical and biotechnological research. Reference proteomes have been selected to provide broad coverage of the tree of life, and constitute a representative cross-section of the taxonomic diversity to be found within UniProtKB.
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