title: Essential role of junctional adhesion molecule-1 in basic fibroblast growth factor-induced endothelial cell migration.
abstract: OBJECTIVE
  Recently, we have shown that blocking of junctional adhesion molecule-1/A (JAM-1/A) inhibits basic fibroblast growth factor (bFGF)-induced angiogenesis. Because the process of endothelial cell proliferation is a key initial step of neovascularization, we studied the effect of functional knockdown of JAM-1 on human umbilical vein endothelial cell (HUVEC) adhesion and migration induced by bFGF.
  
  
  RESULTS
  We introduced small interfering RNAs specific to JAM-1 in HUVECs, stimulated them with bFGF, and studied the resultant adhesion and migration of these cells on vitronectin and fibronectin. We show that depletion of JAM-1 inhibits bFGF-induced HUVEC migration specifically on vitronectin. This inhibition is not attributable to the failure of junctional organization, because expression and distribution of other junctional proteins remained unaffected. This inhibition was in fact attributed to an inability of JAM-1-depleted HUVECs to adhere and spread on vitronectin. Furthermore, we find that JAM-1-depleted HUVECs failed to activate extracellular signal-related kinase (ERK) in response to bFGF treatment.
  
  
  CONCLUSIONS
  Our results show that JAM-1 is required for the bFGF-induced ERK activation that leads to endothelial cell migration on vitronectin. These data thus implicate JAM-1 as an integral part of both bFGF and ERK signaling pathways in endothelial cells.
authors.affiliation: Department of Biological Sciences, University of Delaware, 329 Wolf Hall, Newark, DE 19716, USA. unaik@udel.edu
authors.forename: Meghna U
authors.initials: MU
authors.lastname: Naik
authors.forename: Deepika
authors.initials: D
authors.lastname: Vuppalanchi
authors.forename: Ulhas P
authors.initials: UP
authors.lastname: Naik
mesh_terms: D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D015536:Down-Regulation / Q000235:genetics; D004730:Endothelium, Vascular / Q000166:cytology / Q000201:enzymology / Q000502:physiology*; D004789:Enzyme Activation / Q000235:genetics; D016222:Fibroblast Growth Factor 2 / Q000037:antagonists & inhibitors / Q000502:physiology*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000235:genetics / Q000502:physiology; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D019108:Tight Junctions / Q000737:chemistry / Q000378:metabolism; D014471:Umbilical Veins / Q000166:cytology; D019096:Vitronectin / Q000378:metabolism
chemical_list: D015815:Cell Adhesion Molecules; C407243:F11R protein, human; D034741:RNA, Small Interfering; D011956:Receptors, Cell Surface; D019096:Vitronectin; D016222:Fibroblast Growth Factor 2; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases