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.
Han
Jang-Il
JI
National Institute of Allergy and Infectious Diseases, National Institutes of Health, 10 Center Dr., Bethesda, MD 20892, USA.
Huang
Ning-Na
NN
Kim
Dong-Uk
DU
Kehrl
John H
JH
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