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Defective migration in Activator of G protein Signaling 3‐null leukocytes in response to CXCL12 and CCL19 stimulation
Author(s) -
Branham-O'Connor Melissa,
Maher Ellen M.,
Zhang Xian,
Lanier Stephen M.,
Blumer Joe B.
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.838.7
Subject(s) - ccl19 , biology , microbiology and biotechnology , chemokine , chemotaxis , chemokine receptor , immune system , receptor , signal transduction , immunology , biochemistry
Activator of G protein Signaling 3 (AGS3/Gpsm1), an accessory protein for G protein signaling, has functional roles in the kidney and CNS. Here we show that AGS3 is also expressed in spleen, thymus and bone marrow‐derived dendritic cells (BMDCs), and is upregulated in B‐ and T lymphocytes and BMDCs upon activation. We also observed that AGS3 – Gαi1 complexes are regulated by chemokine receptor activation and AGS3 appears to form a chemokine‐regulated, Gαi‐dependent complex with CXCR4 and CCR7 suggesting that AGS3 may integrate signals emanating from chemokine receptors. As part of a broad effort to define the extent of functional diversity of AGS‐regulated events in vivo , we generated AGS3 null mice. Defects in Gαi signaling effect lymphocyte differentiation and motility; therefore, we measured lymphocyte populations as well as chemokine‐directed chemotaxis of lymphocytes and BMDCs from wild‐type and AGS3‐null mice. We discovered defects in chemotaxis of AGS3‐null BMDCs as well as purified B‐ and T lymphocytes. This defect is not due to alterations in receptor expression, as WT and AGS3‐null cells appear to express similar levels of CXCR4. These studies indicate a role for AGS3 and other GPR proteins in the regulation of G‐protein signaling in the immune system, providing unexpected venues for the potential development of therapeutic agents that modulate immune function by targeting these regulatory mechanisms.