Notch and integrin affinity: a sticky situation.
The Notch pathway is a conserved signal transduction system that mediates intercellular signaling to regulate cell fate decisions in various tissues. Dysregulation of Notch activity results in various disorders, including cardiovascular diseases and cancer. Notch regulates cell fate through a number of mechanisms that include control of cell proliferation, survival, migration, and differentiation. Notch activation increases vascular endothelial cell adhesion through the enhancement of beta(1) integrin affinity for fibronectin, collagens I and IV, and vitronectin without altering the abundance of beta(1) integrin at the cell surface. A study now suggests that this Notch-dependent increase in beta(1) integrin affinity occurs through the activation of the small guanosine triphosphate (GTP)-binding protein, R-Ras. It is proposed that Notch-dependent activation of R-Ras reverses H-Ras-mediated suppression of integrin affinity. Activation of R-Ras by Notch may be triggered by a noncanonical CSL (CBF1 or RBP-Jkappa in vertebrates, Suppressor of Hairless in Drosophila, Lag-1 in Caenorhabditis elegans)-independent pathway. Because R-Ras is selectively distributed in vascular cells, these findings are of particular importance in understanding the effector functions of Notch in the vascular system.
Karsan
Aly
A
Department of Pathology and Laboratory Medicine, British Columbia Cancer Agency, Vancouver, British Columbia V6K 2Z4, Canada. akarsan@bccrc.ca
D000818:Animals; D017173:Caenorhabditis elegans / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000378:metabolism / Q000473:pathology; D002448:Cell Adhesion; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival; D004330:Drosophila / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D006801:Humans; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein / Q000378:metabolism; D019012:Integrin beta1 / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction; D018631:ras Proteins / Q000378:metabolism
D016326:Extracellular Matrix Proteins; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; D019012:Integrin beta1; D051880:Receptors, Notch; D018631:ras Proteins