title: Regulation of endothelial cell morphogenesis by the protein kinase D (PKD)/glycogen synthase kinase 3 (GSK3)β pathway.
abstract: Vascular morphogenesis is a key process for development, reproduction, and pathogenesis. Thus understanding the mechanisms of this process is of pathophysiological importance. Despite the fact that collagen I is the most abundant and potent promorphogenic molecule known, the molecular mechanisms by which this protein regulates endothelial cell tube morphogenesis are still unclear. Here we provide strong evidence that collagen I induces tube morphogenesis by inhibiting glycogen synthase kinase 3β (GSK3β). Further mechanistic studies revealed that GSK3β activity is regulated by protein kinase D (PKD). PKD inhibited GSK3β activity, which was required for collagen I-induced endothelial tube morphogenesis. We also found that GSK3β regulated trafficking of integrin α(2)β(1) in a Rab11-dependent manner. Taken together, our studies highlight the important role of PKD in the regulation of collagen I-induced vascular morphogenesis and show that it is mediated by the modulation of GSK3β activity and integrin α(2)β(1) trafficking.
authors.affiliation: Dept. of Cancer and Cell Biology, Univ. of Cincinnati, College of Medicine, Cincinnati, OH 45267, USA.
authors.forename: Sejeong
authors.initials: S
authors.lastname: Shin
authors.forename: Laura
authors.initials: L
authors.lastname: Wolgamott
authors.forename: Sang-Oh
authors.initials: SO
authors.lastname: Yoon
mesh_terms: D042783:Endothelial Cells / Q000201:enzymology*; D038362:Glycogen Synthase Kinase 3 / Q000502:physiology*; D000071679:Glycogen Synthase Kinase 3 beta; D057809:HEK293 Cells; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D038982:Integrin alpha2beta1 / Q000502:physiology*; D009024:Morphogenesis / Q000502:physiology*; D011493:Protein Kinase C / Q000502:physiology*; D021381:Protein Transport / Q000502:physiology; D015398:Signal Transduction
chemical_list: D038982:Integrin alpha2beta1; C089212:protein kinase D; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D011493:Protein Kinase C; D038362:Glycogen Synthase Kinase 3