|
|
|
|
|
|
|
|
|||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | |||||
Journal of Cell Science, Vol 113, Issue 9 1525-1534, Copyright © 2000 by Company of Biologists
JOURNAL ARTICLES |
W Li and G Keller
Department of Pharmacokinetics and Metabolism, Genentech, Inc., South San Francisco, CA 94080, USA.
Vascular endothelial growth factor (VEGF) is a multifunctional cytokine that plays a prominent role in normal vascular biology and pathology. In an experimental wound model, the mechanical disruption of monolayers of cultured endothelial cells resulted in two phenotypically distinct cell subpopulations in which VEGF was internalized by alternative endocytotic pathways and delivered to different subcellular compartments. In the cells away from the wound, VEGF was internalized via the classical receptor-mediated endocytosis pathway and accumulated in the endosomal compartment, whereas in the cells situated at the edges of a wound, VEGF was rapidly taken up and translocated to the nucleus. VEGF internalization and subsequent nuclear accumulation only occurred for a short period of time after the wounding and was specifically abolished by antibodies that bind to the KDR binding site of VEGF. In the cells with VEGF nuclear accumulation, the levels of wound healing related proteins, such as Factor VIII (FVIII), tissue factor (TF) and tissue plasminogen activator, rapidly and dramatically increased compared to the cells that internalized VEGF via the classical endocytotic pathway. The increase in FVIII and TF was abolished when the nuclear transport is blocked. These data suggest that nuclear VEGF accumulation may be involved in modulating the levels of the proteins of the coagulation and fibrinolysis pathways.
This article has been cited by other articles:
|
|
 |
|
  Y. Oh, R. S. Herbst, H. Burris, A. Cleverly, L. Musib, M. Lahn, and G. Bepler Enzastaurin, an Oral Serine/Threonine Kinase Inhibitor, As Second- or Third-Line Therapy of Non-Small-Cell Lung Cancer J. Clin. Oncol., March 1, 2008; 26(7): 1135 - 1141. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Calvani, D. Trisciuoglio, C. Bergamaschi, R. H. Shoemaker, and G. Melillo Differential Involvement of Vascular Endothelial Growth Factor in the Survival of Hypoxic Colon Cancer Cells Cancer Res., January 1, 2008; 68(1): 285 - 291. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Mitola, B. Brenchio, M. Piccinini, L. Tertoolen, L. Zammataro, G. Breier, M. T. Rinaudo, J. den Hertog, M. Arese, and F. Bussolino Type I Collagen Limits VEGFR-2 Signaling by a SHP2 Protein-Tyrosine Phosphatase-Dependent Mechanism 1 Circ. Res., January 6, 2006; 98(1): 45 - 54. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. N. Re Implications of intracrine hormone action for physiology and medicine Am J Physiol Heart Circ Physiol, March 1, 2003; 284(3): H751 - H757. [Full Text] [PDF]
|
|
|
|
 |
|
 S. Olsnes, O. Klingenberg, and A. Wiedlocha Transport of Exogenous Growth Factors and Cytokines to the Cytosol and to the Nucleus Physiol Rev, January 1, 2003; 83(1): 163 - 182. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B.C. Kuenen, M. Levi, J.C.M. Meijers, A.K. Kakkar, V.W.M. van Hinsbergh, P.J. Kostense, H.M. Pinedo, and K. Hoekman Analysis of Coagulation Cascade and Endothelial Cell Activation During Inhibition of Vascular Endothelial Growth Factor/Vascular Endothelial Growth Factor Receptor Pathway in Cancer Patients Arterioscler. Thromb. Vasc. Biol., September 1, 2002; 22(9): 1500 - 1505. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. T. Rissanen, I. Vajanto, M. O. Hiltunen, J. Rutanen, M. I. Kettunen, M. Niemi, P. Leppanen, M. P. Turunen, J. E. Markkanen, K. Arve, et al. Expression of Vascular Endothelial Growth Factor and Vascular Endothelial Growth Factor Receptor-2 (KDR/Flk-1) in Ischemic Skeletal Muscle and Its Regeneration Am. J. Pathol., April 1, 2002; 160(4): 1393 - 1403. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. C. Kuenen, L. Rosen, E. F. Smit, M. R.N. Parson, M. Levi, R. Ruijter, H. Huisman, M. A. Kedde, P. Noordhuis, W. J.F. van der Vijgh, et al. Dose-Finding and Pharmacokinetic Study of Cisplatin, Gemcitabine, and SU5416 in Patients With Solid Tumors J. Clin. Oncol., March 15, 2002; 20(6): 1657 - 1667. [Abstract] [Full Text] [PDF]
|
|
