Premium
RACK1 negatively regulates SDF1α/CXCL12‐stimulated chemotaxis of Jurkat cells
Author(s) -
Chen Songhai,
Lin Fang,
Hamm Heidi E.
Publication year - 2006
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.20.4.a696-d
Subject(s) - jurkat cells , chemotaxis , microbiology and biotechnology , signal transduction , phospholipase c , biology , gq alpha subunit , chemokine receptor , receptor , chemokine , chemistry , t cell , g protein , biochemistry , immunology , immune system
We showed previously that R eceptor for A ctivated C K inase 1 (RACK1) binds to the signal transfer region of Gβγ and selectively inhibits the activation of a subclass of Gβγ effectors such as phospholipase C β2 (PLCβ2). Here we investigated the functional role of RACK1 in SDF1α/CXCL12‐stimulated chemotaxis of Jurkat cells, a response mediated by the chemokine receptor CXCR4 through Gβγ. We showed by co‐immunoprecipitation studies that endogenous RACK1 forms a complex with Gβγ in Jurkat cells upon the activation of the native receptor CXCR4 via SDF1α/CXCL12. Moreover, RACK1 co‐localizes with Gβγ in the pseudopode when Jurkat cells are stimulated with SDF1α/CXCL12 and polarize. Interestingly, inhibiting RACK1 expression by siRNAs significantly enhances SDF1α/CXCL12‐stimulated chemotaxis, whereas overexpression of full‐length RACK1 or a fragment of RACK1 that specifically binds Gβγ inhibits the cell migration. SDF1α/CXCL12 stimulates multiple signaling pathways in Jurkat cells including phospholipase C, PI3K, MAPKs and Src. However, only the activation of phospholipase C and PI3K is found to be associated with chemotaxis. Based on these findings, we propose that RACK1 may negatively regulate the chemotactic responses of Jurkat cells by selectively modulating signaling pathways downstream of Gβγ. This hypothesis is currently under investigation.