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

Lattin, J. E., Greenwood, K. P., Daly, N. L., Kelly, G, Zidar, D. A., Clark, R. J., Thomas, W. G., Kellie, Stuart, Craik, D. J., Hume, D. A. and Sweet, M. J. (2009) Beta-arrestin 2 is required for complement C1q expression in macrophages and constrains factor-independent survival. Molecular Immunology, 47 2-3: 340-347.


Author Lattin, J. E.
Greenwood, K. P.
Daly, N. L.
Kelly, G
Zidar, D. A.
Clark, R. J.
Thomas, W. G.
Kellie, Stuart
Craik, D. J.
Hume, D. A.
Sweet, M. J.
Title Beta-arrestin 2 is required for complement C1q expression in macrophages and constrains factor-independent survival
Journal name Molecular Immunology  (ERA 2012 Listed)    (ERA 2010 Rank B)   Check publisher's open access policy
Publication date 2009-12
Sub-type Article
Year available 2009
DOI 10.1016/j.molimm.2009.09.012
Volume number 47
Issue number 2-3
ISSN 0161-5890
Start page 340
End page 347
Total pages 8
Editor M. R. Daha
Place of publication Oxford, England, U. K.
Publisher Pergamon Press (Elsevier Science)
Collection year 2010
Language eng
Subject C1
970111 Expanding Knowledge in the Medical and Health Sciences
1107 Immunology
110707 Innate Immunity
Abstract 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.
Keyword Monocyte/macrophage
Complement
Inflammation
Systemic lupus erythematosus
Signal transduction
SYSTEMIC-LUPUS-ERYTHEMATOSUS
SIGNAL-REGULATED KINASES
APOPTOTIC CELLS
INNATE IMMUNITY
GENE-EXPRESSION
MAPK ACTIVATION
BETA-ARRESTIN2
PATHWAY
PROLIFERATION
RECEPTORS
Q-Index Code C1
Q-Index Status Confirmed Code

 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 5 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 6 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Access Statistics: 64 Abstract Views  -  Detailed Statistics
Created: Sun, 10 Jan 2010, 00:03:07 EST