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Arterioscler Thromb Vasc Biol. 2009 Sep;29(9):1376-82. doi: 10.1161/ATVBAHA.109.191585. Epub 2009 Jun 11.

Lysophosphatidylcholine activates a novel PKD2-mediated signaling pathway that controls monocyte migration.

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1
Department of Pathobiology, University of Tennessee College of Veterinary Medicine, Knoxville, TN 37996, USA.

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.

PMID:
19520973
PMCID:
PMC3073140
DOI:
10.1161/ATVBAHA.109.191585
[Indexed for MEDLINE]
Free PMC Article
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