PMID- 16565322 OWN - NLM STAT- MEDLINE DCOM- 20060810 LR - 20071115 IS - 0741-5400 (Print) IS - 0741-5400 (Linking) VI - 79 IP - 6 DP - 2006 Jun TI - RGS1 and RGS13 mRNA silencing in a human B lymphoma line enhances responsiveness to chemoattractants and impairs desensitization. PG - 1357-68 AB - Chemokines bind receptors that are members of the G-protein-coupled receptor family. Chemokine receptors transduce intracellular signals by activating heterotrimeric G-proteins. Acting to limit and modulate heterotrimeric G-protein signaling is a family of proteins, termed regulator of G-protein signaling (RGS). Two of these proteins, RGS1 and RGS13, are well-expressed in germinal center B cells and many Burkitt's lymphoma cell lines. Reducing RGS13 and to a lesser extent RGS1 expression in a Burkitt's lymphoma cell line enhances responsiveness to two chemokines, CXC chemokine ligand 12 (CXCL12) and CXCL13, and reducing both mRNAs augments the responses more dramatically. The double knock-down (KD) cells respond better to restimulation with CXCL12 or CXCL13 after a primary stimulation with CXCL12 than do the control cells. The double-KD cells also exhibit a greater propensity to polarize and to develop multiple small lamellipodia. These results indicate that RGS1 and RGS13 act together to regulate chemokine receptor signaling in human germinal center B lymphocytes and provide evidence that they contribute significantly to the rapid desensitization of the signaling pathway. FAU - Han, Jang-Il AU - Han JI AD - National Institute of Allergy and Infectious Diseases, National Institutes of Health, 10 Center Dr., Bethesda, MD 20892, USA. FAU - Huang, Ning-Na AU - Huang NN FAU - Kim, Dong-Uk AU - Kim DU FAU - Kehrl, John H AU - Kehrl JH LA - eng PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20060324 PL - England TA - J Leukoc Biol JT - Journal of leukocyte biology JID - 8405628 RN - 0 (CXCL12 protein, human) RN - 0 (Chemokine CXCL12) RN - 0 (Chemokines, CXC) RN - 0 (Platelet Activating Factor) RN - 0 (RGS Proteins) RN - 0 (RGS1 protein, human) RN - 0 (RGS13 protein, human) RN - 0 (RNA, Messenger) RN - 0 (Recombinant Fusion Proteins) SB - IM MH - B-Lymphocytes/*drug effects/physiology MH - Burkitt Lymphoma/pathology MH - Cell Line, Tumor/drug effects MH - Chemokine CXCL12 MH - Chemokines, CXC/pharmacology MH - Chemotaxis/*drug effects MH - Genetic Vectors/genetics MH - Germinal Center/*cytology MH - Humans MH - Lentivirus/genetics MH - Platelet Activating Factor/pharmacology MH - RGS Proteins/genetics/*physiology MH - *RNA Interference MH - RNA, Messenger/*antagonists & inhibitors/genetics MH - Recombinant Fusion Proteins/pharmacology MH - Reverse Transcriptase Polymerase Chain Reaction MH - Signal Transduction/drug effects/physiology EDAT- 2006/03/28 09:00 MHDA- 2006/08/11 09:00 CRDT- 2006/03/28 09:00 PHST- 2006/03/28 09:00 [pubmed] PHST- 2006/08/11 09:00 [medline] PHST- 2006/03/28 09:00 [entrez] AID - jlb.1105693 [pii] AID - 10.1189/jlb.1105693 [doi] PST - ppublish SO - J Leukoc Biol. 2006 Jun;79(6):1357-68. doi: 10.1189/jlb.1105693. Epub 2006 Mar 24.