RGS1 and RGS13 mRNA silencing in a human B lymphoma line enhances responsiveness to chemoattractants and impairs desensitization.
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.
National Institute of Allergy and Infectious Diseases, National Institutes of Health, 10 Center Dr., Bethesda, MD 20892, USA.
Jang-Il
JI
Han
Ning-Na
NN
Huang
Dong-Uk
DU
Kim
John H
JH
Kehrl
D001402:B-Lymphocytes / Q000187:drug effects* / Q000502:physiology; D002051:Burkitt Lymphoma / Q000473:pathology; D045744:Cell Line, Tumor / Q000187:drug effects; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000494:pharmacology; D002633:Chemotaxis / Q000187:drug effects*; D005822:Genetic Vectors / Q000235:genetics; D018858:Germinal Center / Q000166:cytology*; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D010972:Platelet Activating Factor / Q000494:pharmacology; D020710:RGS Proteins / Q000235:genetics / Q000502:physiology*; D034622:RNA Interference; D012333:RNA, Messenger / Q000037:antagonists & inhibitors* / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D010972:Platelet Activating Factor; D020710:RGS Proteins; C080831:RGS1 protein, human; C456322:RGS13 protein, human; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins