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https://hdl.handle.net/2440/27583
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Type: | Journal article |
Title: | Transactivation of CXCR4 by the insulin-like growth factor-1 receptor (IGF-1R) in human MDA-MB-231 breast cancer epithelial cells |
Author: | Akekawatchai, C. Holland, J. Kochetkova, M. Wallace, J. McColl, S. |
Citation: | Journal of Biological Chemistry, 2005; 280(48):39701-39708 |
Publisher: | Amer Soc Biochemistry Molecular Biology Inc |
Issue Date: | 2005 |
ISSN: | 0021-9258 1083-351X |
Statement of Responsibility: | Chareeporn Akekawatchai, Jane D. Holland, Marina Kochetkova, John C. Wallace and Shaun R. McColl |
Abstract: | In the multimolecular environment in tissues and organs, crosstalk between growth factor and G protein-coupled receptors is likely to play an important role in both normal and pathological responses. In this report, we demonstrate transactivation of the chemokine receptor CXCR4 by the growth factor insulin-like growth factor (IGF)-1 is required for IGF-1-induced cell migration in metastatic MDA-MB-231 cells. The induction of chemotaxis in MDAMB- 231 cells by IGF-1 was inhibited by pretreatment of the cells with pertussis toxin (PTX) and by RNAi-mediated knockdown of CXCR4. Transactivation of the CXCR4 pathway by IGF-1 occurred independently of CXCL12, the chemokine ligand of CXCR4. Neither CXCR4 knockdown nor PTX had any effect on the ability of IGF-1 to activate IGF-1R, suggesting thatCXCR4andGproteins are activated subsequent to, or independently of, phosphorylation of IGF-1R by IGF-1. Coprecipitation studies revealed the presence of a constitutive complex containing IGF-1R, CXCR4, and theGprotein subunits, Giα2 and Gß, and stimulation of MDA-MB-231 cells with IGF-1 led to the release of Giα2 and Gß from CXCR4. Based on our findings, we propose that CXCR4 constitutively forms a complex with IGF-1R in MDA-MB-231 cells, and that this interaction allows IGF-1 to activate migrational signaling pathways through CXCR4, Giα2 and Gß. |
Keywords: | Cell Line Cell Line, Tumor Hybridomas Animals Mice, Inbred BALB C Humans Mice Retroviridae Breast Neoplasms Neoplasm Metastasis GTP-Binding Proteins GTP-Binding Protein alpha Subunits, Gi-Go Pertussis Toxin Receptor, IGF Type 1 Insulin-Like Growth Factor I GTP-Binding Protein beta Subunits Receptors, CXCR4 Ligands Blotting, Western Flow Cytometry Immunoprecipitation Signal Transduction Cell Movement Chemotaxis RNA Interference Protein Binding Dose-Response Relationship, Drug Time Factors Transcriptional Activation |
Description: | The definitive version can be found at http://www.jbc.org/ |
DOI: | 10.1074/jbc.M509829200 |
Published version: | http://www.jbc.org/cgi/content/abstract/280/48/39701 |
Appears in Collections: | Aurora harvest 6 Molecular and Biomedical Science publications |
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