Co-operative Cdc42 and Rho signalling mediates ephrinB-triggered endothelial cell retraction
| Autor: | Gillian Groeger, Catherine D. Nobes |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Umbilical Veins
macromolecular substances CDC42 Biology Endocytosis Heterocyclic Compounds 4 or More Rings Biochemistry Humans Biotinylation cdc42 GTP-Binding Protein Cytoskeleton Molecular Biology Rho-associated protein kinase Cells Cultured Receptors Eph Family Kinase GTPase-Activating Proteins Erythropoietin-producing hepatocellular (Eph) receptor Cell Biology Immunohistochemistry Rho Factor Cell biology Endothelial stem cell Endothelium Vascular Signal transduction Research Article Signal Transduction |
| Zdroj: | Biochemical Journal. 404:23-29 |
| ISSN: | 1470-8728 0264-6021 |
| DOI: | 10.1042/bj20070146 |
| Popis: | Cell repulsion responses to Eph receptor activation are linked to rapid actin cytoskeletal reorganizations, which in turn are partially mediated by Rho–ROCK (Rho kinase) signalling, driving actomyosin contractility. In the present study, we show that Rho alone is not sufficient for this repulsion response. Rather, Cdc42 (cell division cycle 42) and its effector MRCK (myotonic dystrophy kinase-related Cdc42-binding kinase) are also critical for ephrinB-induced cell retraction. Stimulation of endothelial cells with ephrinB2 triggers rapid, but transient, cell retraction. We show that, although membrane retraction is fully blocked by blebbistatin (a myosin-II ATPase inhibitor), it is only partially blocked by inhibiting Rho–ROCK signalling, suggesting that there is ROCK-independent signalling to actomyosin contractility downstream of EphBs. We find that a combination of either Cdc42 or MRCK inhibition with ROCK inhibition completely abolishes the repulsion response. Additionally, endocytosis of ephrin–Eph complexes is not required for initial cell retraction, but is essential for subsequent Rac-mediated re-spreading of cells. Our data reveal a complex interplay of Rho, Rac and Cdc42 in the process of EphB-mediated cell retraction–recovery responses. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|