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A role of the protein Cbl in FGF-2-induced angiogenesis in murine brain endothelial cells
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
Center for Matrix Biology, Department of Medicine, Dana 513, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Ave, Boston, 02215 Massachusetts, USA.
2005 (English)In: Cellular Signalling, ISSN 0898-6568, E-ISSN 1873-3913, Vol. 17, no 11, 1433-1438 p.Article in journal (Refereed) Published
Abstract [en]

The Cbl protein functions both as a multivalent adaptor and a negative regulator of receptor tyrosine kinases (RTKs), the latter by directing polyubiquitination of RTKs. To study the function of Cbl in endothelial cell signalling and angiogenesis, wild-type Cbl and tyrosine kinase binding (TKB) domain mutated Cbl (G306E) were overexpressed in murine immortalised brain endothelial (IBE) cells. Wild-type Cbl cells exhibited enhanced proliferation in low serum compared with the control and G306E Cbl cells. Furthermore, up-regulated phosphorylation of fibroblast growth factor receptor 1 (FGFR-1) and Akt were observed in wild-type Cbl cells upon FGF-2 stimulation. A Cbl TKB domain mutant, G306E, disrupted the phosphorylation of the FGFR-1 but not that of FRS2. In the tubular morphogenesis assay, cells expressing wild-type Cbl initially formed tubular structures. These showed decreased stability and converted into cell aggregates, possibly due to a failure to cease proliferating. Our data support the idea that the wild-type Cbl cells exhibit enhanced proliferation, and thus lose their ability to differentiate appropriately. The present study reveals a role of the Cbl protein in FGF-2 dependent signalling in endothelial cells by its destabilisation of tubular structures.

Place, publisher, year, edition, pages
2005. Vol. 17, no 11, 1433-1438 p.
Keyword [en]
Animals, Brain/blood supply, Cell Differentiation, Cell Line; Transformed, Cell Proliferation, Culture Media, Endothelial Cells/cytology/*physiology, Fibroblast Growth Factor 2/*physiology, Mice, Mutation, Neovascularization; Physiologic, Phosphorylation, Proto-Oncogene Proteins c-cbl/biosynthesis/genetics/*physiology, Receptor; Fibroblast Growth Factor; Type 1/genetics/metabolism, Research Support; Non-U.S. Gov't, Serum, Signal Transduction
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-79781DOI: 10.1016/j.cellsig.2005.03.005PubMedID: 16125056OAI: oai:DiVA.org:uu-79781DiVA: diva2:107694
Available from: 2006-04-13 Created: 2006-04-13 Last updated: 2017-12-14Bibliographically approved

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Welsh, Michael

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