Transactivation of CXCR4 by the insulin-like growth factor-1 receptor (IGF-1R) in human MDA-MB-231 breast cancer epithelial cells
Date
2005
Authors
Akekawatchai, C.
Holland, J.
Kochetkova, M.
Wallace, J.
McColl, S.
Editors
Advisors
Journal Title
Journal ISSN
Volume Title
Type:
Journal article
Citation
Journal of Biological Chemistry, 2005; 280(48):39701-39708
Statement of Responsibility
Chareeporn Akekawatchai, Jane D. Holland, Marina Kochetkova, John C. Wallace and Shaun R. McColl
Conference Name
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.
School/Discipline
Dissertation Note
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