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Phospholipase Cgamma2 mediates RANKL-stimulated lymph node organogenesis and osteoclastogenesis. J Biol Chem 2008 Oct 24;283(43):29593-601

Date

08/30/2008

Pubmed ID

18728019

Pubmed Central ID

PMC2570883

DOI

10.1074/jbc.M802493200

Scopus ID

2-s2.0-57649174473   21 Citations

Abstract

Phospholipase Cgamma2 (PLCgamma2) is an important signaling effector of multiple receptors in the immune system. Here we show that PLCgamma2-deficient mice displayed impaired lymph node organogenesis but normal splenic structure and Peyer's patches. Receptor activator of NF-kappaB ligand (RANKL) is a tumor necrosis factor family cytokine and is essential for lymph node organogenesis. Importantly, PLCgamma2 deficiency severely impaired RANKL signaling, resulting in marked reduction of RANKL-induced activation of MAPKs, p38 and JNK, but not ERK. The lack of PLCgamma2 markedly diminished RANKL-induced activation of NF-kappaB, AP-1, and NFATc1. Moreover, PLCgamma2 deficiency impaired RANKL-mediated biological function, leading to failure of the PLCgamma2-deficient bone marrow macrophage precursors to differentiate into osteoclasts after RANKL stimulation. Re-introduction of PLCgamma2 but not PLCgamma1 restores RANKL-mediated osteoclast differentiation of PLCgamma2-deficient bone marrow-derived monocyte/macrophage. Taken together, PLCgamma2 is essential for RANK signaling, and its deficiency leads to defective lymph node organogenesis and osteoclast differentiation.

Author List

Chen Y, Wang X, Di L, Fu G, Chen Y, Bai L, Liu J, Feng X, McDonald JM, Michalek S, He Y, Yu M, Fu YX, Wen R, Wu H, Wang D

Author

Demin Wang PhD Assistant Professor in the Microbiology and Immunology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Cell Differentiation
Cytokines
Extracellular Signal-Regulated MAP Kinases
Lymph Nodes
Mice
Mice, Transgenic
Models, Biological
Organogenesis
Osteoclasts
Phospholipase C gamma
RANK Ligand
Signal Transduction
Spleen
p38 Mitogen-Activated Protein Kinases
jenkins-FCD Prod-469 c3fc8ab87196149f9b23743c01b947d47e7319e5