- Paper Report
- Open Access
Arthritis and G-protein-coupled receptor regulation
- Jose L Pablos1
© Biomed Central Ltd 2001
- Received: 28 March 2001
- Accepted: 26 July 2001
- Published: 26 July 2001
- protein kinases
G-protein-coupled receptors (GPCRs) mediate cellular responses to a large variety of mediators of immune and inflammatory processes such as chemokines, prostanoids or hormones. GPCR signal transduction through G proteins is tightly regulated by agonist-induced desensitization. Protein kinases, phosphatases, endocytosis and recycling play various roles in direct and cross-desensitization of these receptors. Natural mechanisms of turning off signaling by GPCRs are potential targets for anti-inflammatory or immunomodulatory therapies. The authors explore the regulation of GPCR kinases (GRKs) and arrestins, the proteins involved in desensitization of GPCRs, during the development of adjuvant arthritis.
During adjuvant arthritis in rats, both T and B cells from secondary immune organs (spleen and lymph nodes) displayed a dramatic reduction in the enzymatic activity and levels of the main GRKs expressed in leukocytes, GRK2, GRK3 and GRK6, while ?-arrestin-1 levels were increased. All proteins returned to normal levels after arthritis resolved. Changes in GRK protein expression occurred at the post-transcriptional level, since no changes in mRNA levels were detected. These changes were specific to secondary lymphoid organs and did not occur in other organs such as thymus, heart or pituitary.
Adjuvant arthritis induction in Lewis rats, analysis of GRK activity in tissue extracts by light-dependent phosphorylation of rhodopsin, northern and western blot
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