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- Title
A role for chemokine receptor transactivation in growth factor signaling.
- Authors
Mira, Emilia; Lacalle, Rosa Ana; González, Manuel A.; Gómez-Moutón, Concepción; Abad, José Luis; Bernad, Antonio; Martínez-A., Carlos; Mañes, Santos
- Abstract
Complex cell responses require the integration of signals delivered through different pathways. We show that insulin-like growth factor (IGF)-I induces specific transactivation of the Gi-coupled chemokine receptor CCR5, triggering its tyrosine phosphorylation and Gαi recruitment. This transactivation occurs via a mechanism involving transcriptional upregulation and secretion of RANTES, the natural CCR5 ligand. CCR5 transactivation is an essential downstream signal in IGF-I-induced cell chemotaxis, as abrogation of CCR5 function with a transdominant-negative KDELccr5A32 mutant abolishes IGF-I- induced migration. The relevance of this transactivation pathway was shown in vivo, as KDELccr5A32 overexpression prevents invasion by highly metastatic tumor cells; conversely, RANTES overexpression confers built-in invasive capacity on a non-invasive tumor cell line. Our results suggest that this extracellular growth factor-chemokine network represents a general mechanism connecting tumorigenesis and inflammation.
- Subjects
CHEMOKINES; TUMORS; CELLS; CHEMOTAXIS; TYROSINE; PHOSPHORYLATION
- Publication
EMBO Reports, 2001, Vol 2, Issue 2, p151
- ISSN
1469-221X
- Publication type
Report
- DOI
10.1093/embo-reports/kve027