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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Ehrenreiter, Karin Baccarini, Manuela Piazzolla, Daniela Leung, Thomas Takeda, Junji Sobczak, Izabela Small, J. Victor Velamoor, Vanishree |
| Description | Author Affiliation: Ehrenreiter K ( Department of Microbiology and Genetics, Max F. Perutz Laboratories, University Departments at the Vienna Biocenter, 1030 Vienna, Austria.) |
| Abstract | Raf kinases relay signals inducing proliferation, differentiation, and survival. The Raf-1 isoform has been extensively studied as the upstream kinase linking Ras activation to the MEK/ERK module. Recently, however, genetic experiments have shown that Raf-1 plays an essential role in counteracting apoptosis, and that it does so independently of its ability to activate MEK. By conditional gene ablation, we now show that Raf-1 is required for normal wound healing in vivo and for the migration of keratinocytes and fibroblasts in vitro. Raf-1–deficient cells show a symmetric, contracted appearance, characterized by cortical actin bundles and by a disordered vimentin cytoskeleton. These defects are due to the hyperactivity and incorrect localization of the Rho-effector Rok-α to the plasma membrane. Raf-1 physically associates with Rok-α in wild-type (WT) cells, and reintroduction of either WT or kinase-dead Raf-1 in knockout fibroblasts rescues their defects in shape and migration. Thus, Raf-1 plays an essential, kinase-independent function as a spatial regulator of Rho downstream signaling during migration. |
| ISSN | 00219525 |
| e-ISSN | 15408140 |
| Journal | The Journal of Cell Biology |
| Issue Number | 6 |
| Volume Number | 168 |
| Language | English |
| Publisher | Rockefeller University Press (United States) |
| Publisher Date | 2005-03-14 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Cell Movement Proto-Oncogene Proteins C-raf Physiology Signal Transduction Rho GTP-Binding Proteins Metabolism Animals Animals, Newborn Apoptosis Blotting, Western COS Cells Cell Adhesion Cell Shape Cells, Cultured Cercopithecus Aethiops Fibroblasts Gene Expression Regulation Keratin-15 Keratin-5 Keratinocytes Keratins Ki-67 Antigen Mice Mice, Transgenic Microscopy, Confocal Precipitin Tests Protein Precursors Genetics Time Factors Wound Healing Research Support, Non-U.S. Gov't Cell Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Medicine |
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