Pamela F. Jones
Regeneron
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Publication
Featured researches published by Pamela F. Jones.
Cell | 1996
Chitra Suri; Pamela F. Jones; Sybill Patan; Sona Bartunkova; Peter C. Maisonpierre; Samuel Davis; Thomas N. Sato; George D. Yancopoulos
Vascular endothelial growth factor (VEGF), which acts via members of a family of endothelial-specific receptor tyrosine kinases, is the only factor that has been shown definitively to play a role in the formation of the embryonic vasculature. Only one other family of receptor tyrosine kinases, comprising TIE1 and TIE2, is largely endothelial cell specific. We have recently cloned a ligand for TIE2, termed Angiopoietin-1. Here we show that mice engineered to lack Angiopoietin-1 display angiogenic deficits reminiscent of those previously seen in mice lacking TIE2, demonstrating that Angiopoietin-1 is a primary physiologic ligand for TIE2 and that it has critical in vivo angiogenic actions that are distinct from VEGF and that are not reflected in the classic in vitro assays used to characterize VEGF. Angiopoietin-1 seems to play a crucial role in mediating reciprocal interactions between the endothelium and surrounding matrix and mesenchyme.
Cell | 1996
Samuel Davis; Thomas H. Aldrich; Pamela F. Jones; Ann Acheson; Debra L Compton; Vivek Jain; Terence E. Ryan; Joanne Bruno; Czeslaw Radziejewski; Peter C. Maisonpierre; George D. Yancopoulos
TIE2 is a receptor-like tyrosine kinase expressed almost exclusively in endothelial cells and early hemopoietic cells and required for the normal development of vascular structures during embryogenesis. We report the identification of a secreted ligand for TIE2, termed Angiopoietin-1, using a novel expression cloning technique that involves intracellular trapping and detection of the ligand in COS cells. The structure of Angiopoietin-1 differs from that of known angiogenic factors or other ligands for receptor tyrosine kinases. Although Angiopoietin-1 binds and induces the tyrosine phosphorylation of TIE2, it does not directly promote the growth of cultured endothelial cells. However, its expression in close proximity with developing blood vessels implicates Angiopoietin-1 in endothelial developmental processes.
Cell | 1995
Trevor N. Stitt; Greg Conn; Martin Goret; Cary Lai; Joanne Bruno; Czeslaw Radzlejewski; Karen Mattsson; John Fisher; David R. Gies; Pamela F. Jones; Piotr Masiakowski; Terence E. Ryan; Nancy J Tobkes; D.H Chen; Peter S. DiStefano; George L. Long; Claudio Basilico; Mitchell Goldfarb; Greg Lemke; David J. Glass; George D. Yancopoulos
We report the identification of ligands for Tyro 3 (alternatively called Sky, rse, brt, or tif) and Axl (alternatively, Ark or UFO), members of a previously orphan family of receptor-like tyrosine kinases. These ligands correspond to protein S, a protease regulator that is a potent anticoagulant, and Gas6, a protein related to protein S but lacking any known function. Our results are reminiscent of recent findings that the procoagulant thrombin, a protease that drives clot formation by cleaving fibrinogen to form fibrin, also binds and activates intracellular signaling via a G protein-coupled cell surface receptor. Proteases and protease regulators that also activate specific cell surface receptors may serve to integrate coagulation with associated cellular responses required for tissue repair and growth, as well as to coordinate protease cascades and associated cellular responses in other systems, such as those involved in growth and remodeling of the nervous system.
Journal of Biological Chemistry | 1998
Bernhard Witzenbichler; Peter C. Maisonpierre; Pamela F. Jones; George D. Yancopoulos; Jeffrey M. Isner
Angiopoietin-1 and its putative natural antagonist, angiopoietin-2, were recently isolated, and the critical role of angiopoietin-1 in embryogenic angiogenesis was demonstrated by targeted gene disruption. Specific biological effects of angiopoietin-1, however, have yet to be defined. In this study we demonstrate that angiopoietin-1, but not angiopoietin-2, is chemotactic for endothelial cells. In contrast, angiopoietin-1 as well as angiopoietin-2 exhibit no proliferative effect on endothelial cells. Excess soluble Tie2, but not Tie1 receptor, abolish the chemotactic response of endothelial cells toward angiopoietin-1. Angiopoietin-2 dose-dependently blocks directed migration toward angiopoietin-1, consistent with the role of angiopoietin-2 as a naturally occurring inhibitor of angiopoietin-1. Fibroblasts stably transfected with Tie2 receptor exhibit chemotactic responses for both angiopoietin-1 and angiopoietin-2. Fibroblasts stably expressing a transfected chimeric receptor consisting of the ectodomain of TrkC fused to the cytoplasmic domain of Tie2 also exhibit a chemotactic response to neurotrophin 3 (NT-3), a specific ligand for TrkC. Endothelial cells are shown to express angiopoietin-2 mRNA and protein, indicating the potential for autocrine activation of angiopoietin/Tie2. Finally, the demonstration that Tie2 as well as angiopoietin-1 are expressed in normal human arteries and veins suggests that the role of angiopoietin/Tie2 may extend beyond embryonic angiogenesis to maintaining integrity of the adult vasculature.
Science | 1997
Peter C. Maisonpierre; Chitra Suri; Pamela F. Jones; Sona Bartunkova; Stanley J. Wiegand; Czeslaw Radziejewski; Debra Compton; Joyce McClain; Thomas H. Aldrich; Nick Papadopoulos; Thomas J. Daly; Samuel Davis; Thomas N. Sato; George D. Yancopoulos
Proceedings of the National Academy of Sciences of the United States of America | 1991
Pamela F. Jones; T Jakubowicz; F J Pitossi; F Maurer; Brian A. Hemmings
Proceedings of the National Academy of Sciences of the United States of America | 1999
David M. Valenzuela; Jennifer Griffiths; Jose Rojas; Thomas H. Aldrich; Pamela F. Jones; Hao Zhou; Joyce McClain; Neal G. Copeland; Debra J. Gilbert; Nancy A. Jenkins; Tammy T. Huang; N. Papadopoulos; Peter C. Maisonpierre; Samuel Davis; George D. Yancopoulos
Archive | 1995
Samuel Davis; Joanne Bruno; Mitchell Goldfarb; Thomas H. Aldrich; Peter C. Maisonpierre; Czeslaw Radziejewski; Pamela F. Jones; George D. Yancopoulos
Archive | 1998
Samuel Davis; Joanne Bruno; Mitchell Goldfarb; Thomas H. Aldrich; Peter C. Maisonpierre; Czeslaw Radziejewski; Pamela F. Jones; George D. Yancopoulos
Journal of Biological Chemistry | 1995
Mirjana Andjelkovic; Pamela F. Jones; Ueli Grossniklaus; Peter Cron; Alexander F. Schier; Mathias Dick; Graeme Bilbe; Brian A. Hemmings