A role of the protein Cbl in FGF-2-induced angiogenesis in murine brain endothelial cells
2005 (English)In: Cellular Signalling, ISSN 0898-6568, E-ISSN 1873-3913, Vol. 17, no 11, 1433-1438 p.Article in journal (Refereed) Published
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.
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
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-79781DOI: 10.1016/j.cellsig.2005.03.005PubMedID: 16125056OAI: oai:DiVA.org:uu-79781DiVA: diva2:107694