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RGS1 and RGS13 mRNA silencing in a human B lymphoma line enhances responsiveness to chemoattractants and impairs desensitization
Author(s) -
Han JangIl,
Huang NingNa,
Kim DongUk,
Kehrl John H.
Publication year - 2006
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.1105693
Subject(s) - biology , desensitization (medicine) , chemotaxis , gene silencing , messenger rna , lymphoma , immunology , microbiology and biotechnology , receptor , gene , genetics
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.