Journal article
RACK1 negatively regulates SDF1α/CXCL12‐stimulated chemotaxis of Jurkat cells
The FASEB journal, Vol.20(4), pp.A696-A697
03/2006
DOI: 10.1096/fasebj.20.4.A696-d
Abstract
We showed previously that Receptor for Activated C Kinase 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.
Details
- Title: Subtitle
- RACK1 negatively regulates SDF1α/CXCL12‐stimulated chemotaxis of Jurkat cells
- Creators
- Songhai Chen - Vanderbilt University Medical CenterFang Lin - Vanderbilt University Medical CenterHeidi E Hamm - Vanderbilt University Medical Center
- Resource Type
- Journal article
- Publication Details
- The FASEB journal, Vol.20(4), pp.A696-A697
- DOI
- 10.1096/fasebj.20.4.A696-d
- ISSN
- 0892-6638
- eISSN
- 1530-6860
- Publisher
- Federation of American Societies for Experimental Biology
- Number of pages
- 1
- Language
- English
- Date published
- 03/2006
- Academic Unit
- Anatomy and Cell Biology; Iowa Neuroscience Institute; Craniofacial Anomalies Research Center; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984071729502771
Metrics
26 Record Views