title: Deferential regulation of placenta growth factor (PlGF)-mediated signal transduction in human primary term trophoblast and endothelial cells.
abstract: Increasing evidence supports that many common obstetrical complications may involve the disruption of normal placental and/or uterine vascular function. Placenta growth factor (PlGF) is an angiogenic factor that is abundantly expressed in the placenta, with primary site of synthesis being trophoblast. Receptors for PlGF include products of the fms-like tyrosine kinase (flt-1) gene which is expressed in several cell types including endothelial cells and trophoblast. PlGF activation of flt-1 in trophoblast induces the stress activated protein kinase (SAPK) signal transduction pathways, JNK (c-Jun-N-Terminal Kinase) and p38, with little induction of the extracellular signal-regulated protein kinase (ERK)-1/2 pathways. In contrast, PlGF induces strong ERK-1/2 activation, but little JNK or p38 responses in human umbilical vein endothelial cells (HUVEC). To better understand the biochemical functions of PlGF in trophoblast, we studied upstream signal regulatory molecules to determine those that are responsible for directing the divergent PlGF signal transduction responses in these cell types. PlGF induced similar activation of Nck and PLC-gamma in trophoblast and HUVEC. In marked contrast, SHP-2 and Gab2 were strongly activated by PlGF in endothelial cells but not trophoblast. These results suggest a general role for Nck and PLC-gamma in mediating PlGF signal transduction responses independent of the different downstream MAPK pathways activated. However, SHP-2 and Gab2 are regulatory molecules involved in the PlGF induction of different terminal pathways in HUVEC and trophoblast.
authors.affiliation: Department of Medical Microbiology and Immunology, Southern Illinois University School of Medicine, Springfield, IL 62794-9626, USA.
authors.forename: J
authors.initials: J
authors.lastname: Arroyo
authors.forename: R J
authors.initials: RJ
authors.lastname: Torry
authors.forename: D S
authors.initials: DS
authors.lastname: Torry
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D015153:Blotting, Western; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D004815:Epidermal Growth Factor / Q000494:pharmacology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D015513:Oncogene Proteins / Q000378:metabolism; D051966:Phospholipase C gamma; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D000072483:Placenta Growth Factor; D011257:Pregnancy Proteins / Q000494:pharmacology / Q000502:physiology*; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D014327:Trophoblasts / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D010738:Type C Phospholipases / Q000378:metabolism; D014471:Umbilical Veins / Q000166:cytology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C490895:GAB2 protein, human; D047908:Intracellular Signaling Peptides and Proteins; C078332:Nck protein; D015513:Oncogene Proteins; C000608036:PGF protein, human; D010750:Phosphoproteins; D011257:Pregnancy Proteins; D000072483:Placenta Growth Factor; D004815:Epidermal Growth Factor; C516724:PTPN11 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases; D010738:Type C Phospholipases; D051966:Phospholipase C gamma