title: Cell proliferation and migration are modulated by Cdk-1-phosphorylated endothelial-monocyte activating polypeptide II.
abstract: BACKGROUND
  Endothelial-Monocyte Activating Polypeptide (EMAP II) is a secreted protein with well-established anti-angiogenic activities. Intracellular EMAP II expression is increased during fetal development at epithelial/mesenchymal boundaries and in pathophysiologic fibroproliferative cells of bronchopulmonary dysplasia, emphysema, and scar fibroblast tissue following myocardial ischemia. Precise function and regulation of intracellular EMAP II, however, has not been explored to date.
  
  
  RESULTS
  Here we show that high intracellular EMAP II suppresses cellular proliferation by slowing progression through the G2M cell cycle transition in epithelium and fibroblast. Furthermore, EMAP II binds to and is phosphorylated by Cdk1, and exhibits nuclear/cytoplasmic partitioning, with only nuclear EMAP II being phosphorylated. We observed that extracellular secreted EMAP II induces endothelial cell apoptosis, where as excess intracellular EMAP II facilitates epithelial and fibroblast cells migration.
  
  
  CONCLUSIONS
  Our findings suggest that EMAP II has specific intracellular effects, and that this intracellular function appears to antagonize its extracellular anti-angiogenic effects during fetal development and pulmonary disease progression.
authors.affiliation: Department of Pediatrics, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, United States of America. margaret.schwarz@utsouthwestern.edu
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Schwarz
authors.forename: Janet
authors.initials: J
authors.lastname: Thornton
authors.forename: Haiming
authors.initials: H
authors.lastname: Xu
authors.forename: Niranjan
authors.initials: N
authors.lastname: Awasthi
authors.forename: Roderich E
authors.initials: RE
authors.lastname: Schwarz
mesh_terms: D000818:Animals; D001665:Binding Sites; D016203:CDC2 Protein Kinase / Q000378:metabolism*; D002453:Cell Cycle / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D016207:Cytokines / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D051379:Mice; D009363:Neoplasm Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D021381:Protein Transport; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D013912:Threonine / Q000378:metabolism
chemical_list: D016207:Cytokines; D009363:Neoplasm Proteins; D016601:RNA-Binding Proteins; C077219:small inducible cytokine subfamily E, member 1; D013912:Threonine; D016203:CDC2 Protein Kinase