Beta-arrestin 2 is required for complement C1q expression in macrophages and constrains factor-independent survival

Lattin, Jane E., Greenwood, Kathryn P., Daly, Norelle L., Kelly, Gregory, Zidar, David A., Clark, Richard J., Thomas, Walter G., Kellie, Stuart, Craik, David J., Hume, David A., and Sweet, Matthew J. (2009) Beta-arrestin 2 is required for complement C1q expression in macrophages and constrains factor-independent survival. Molecular Immunology, 47 (2-3). pp. 340-347.

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The beta-arrestins (ARRB1 and ARRB2) regulate G-protein coupled receptor (GPCR) dependent- and independent-signaling pathways and are ubiquitously expressed. Here we show that ARRB2 mRNA and protein expression is enriched in macrophages, and that it regulates complement C1q expression and cell survival. Basal and Toll-like receptor (TLR) inducible expression of mRNAs encoding the complement subcomponents C1qa, C1qb and C1qc was greatly reduced in bone marrow-derived macrophages (BMM) from ARRB2-deficient, but not ARRB1-deficient mice, while factor-independent survival of ARRB2(-/-) BMM was enhanced compared to wildtype BMM. TatARRB2(23), a cell-permeable peptide that contains the MAPK JNK-binding motif from within the ARRB2 C-domain, impaired ARRB2 interaction with JNK3, down-regulated C1q expression and permitted factor-independent survival in BMM, thus suggesting that this peptide antagonises ARRB2 function in macrophages. In addition, TatARRB2(23) transiently activated the phosphorylation of JNK and ERK, but not p38 in BMM. These data imply that ARRB2 acts to limit JNK/ERK activation and survival in macrophages, but is required for basal and TLR-inducible complement C1q expression. Given that loss of C1q function is strongly associated with the development of systemic lupus erythematosus, ARRB2 may act to limit the development of autoimmune disease.

Item ID: 27060
Item Type: Article (Research - C1)
ISSN: 1872-9142
Keywords: monocyte/macrophage; complement; inflammation; systemic lupus erythematosus; signal transduction
Date Deposited: 11 Jun 2013 06:25
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110703 Autoimmunity @ 100%
SEO Codes: 97 EXPANDING KNOWLEDGE > 970111 Expanding Knowledge in the Medical and Health Sciences @ 100%
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