title: Lysophosphatidylcholine activates a novel PKD2-mediated signaling pathway that controls monocyte migration.
abstract: OBJECTIVE
  Monocyte activation and migration are crucial events in the development of atherosclerosis and other inflammatory diseases. This study examined the role of protein kinase D (PKD) in monocyte migration. Method and Results- PKD2 is the predominant isoform of PKD expressed in monocytic THP-1 cells and primary human monocytes. Lysophosphatidylcholine (lysoPC), a prominent component of oxidized low-density lipoprotein, induces rapid and marked PKD activation in these cells. Using multiple approaches, including dominant-negative mutants and small interfering RNA knock-down, we found that lysoPC-induced PKD2 activation was required for the activation of both ERK and p38 MAPK. p38 MAPK mediation of lysoPC-induced monocytic cell migration was reported previously; our results reveal that the lysoPC-induced PKD2-p38 pathway controls monocyte migration.
  
  
  CONCLUSIONS
  This study provides the first evidence that (1) lysoPC activates PKD, (2) PKD2 has a novel role in p38 activation, and (3) the PKD2-activated p38 pathway is responsible for lysoPC-induced migration of THP-1 cells and human monocytes. Thus, PKD is a novel and functional intracellular regulator in both lysoPC signaling and monocyte migration. These results suggest a new role for PKD2 in the development of atherosclerosis and other inflammatory diseases.
authors.affiliation: Department of Pathobiology, University of Tennessee College of Veterinary Medicine, Knoxville, TN 37996, USA.
authors.forename: Mingqi
authors.initials: M
authors.lastname: Tan
authors.forename: Feng
authors.initials: F
authors.lastname: Hao
authors.forename: Xuemin
authors.initials: X
authors.lastname: Xu
authors.forename: Guy M
authors.initials: GM
authors.lastname: Chisolm
authors.forename: Mei-Zhen
authors.initials: MZ
authors.lastname: Cui
mesh_terms: D018797:Cell Cycle Proteins / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D008244:Lysophosphatidylcholines / Q000378:metabolism*; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D037342:Pertussis Toxin / Q000494:pharmacology; D000091283:Protein Kinase D2; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014162:Transfection; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; C115270:G2A receptor; D008244:Lysophosphatidylcholines; D000091283:Protein Kinase D2; D043562:Receptors, G-Protein-Coupled; D037342:Pertussis Toxin; D011494:Protein Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D019204:GTP-Binding Proteins