Crosstalk between the extracellular domain of the ErbB2 receptor and IGF-1 receptor signaling |
| |
Authors: | Belaus Andrea Merkle Christian Fritsche Michael Groner Bernd |
| |
Affiliation: | Georg Speyer Haus, Institute for Biomedical Research, Paul Ehrlich Street 42–44, 60596, Frankfurt am Main, Germany |
| |
Abstract: | Insulin-like growth factor 1 receptor (IGF-1R) plays an important role in cell growth and malignant transformation. To investigate IGF-1R-dependent signaling events and its effects on apoptosis induction and cellular proliferation, we generated a constitutively active, ligand-independent IGF-1R variant. We fused the cytoplasmic domain of the IGF-1R to the extracellular and transmembrane domains of the oncogenic ErbB2 receptor (ErbB2V→E/IGF-1). A fusion protein in which the wild-type sequence of the ErbB2 receptor was used, served as a control (ErbB2V/IGF-1R). ErbB2V/IGF-1R, ErbB2V→E/IGF-1R and IGF-1R were stably transfected into interleukin 3 (IL-3)-dependent BaF/3 cells. ErbB2V→E/IGF-1R expressing cells exhibited ligand-independent, constitutive tyrosine phosphorylation of the receptor fusion protein. Constitutively, activated ErbB2V→E/IGF-1R conferred IL-3 independence for growth and survival to the transfected BaF/3 cells. Constitutive activation of the IGF-1R results in cellular growth and protection against apoptosis upon IL-3 withdrawal in BaF/3 cells. |
| |
Keywords: | Insulin-like growth factor receptor (IGF-1R) ErbB2 receptor Receptor fusion protein Tyrosine phosphorylation Apoptosis Cell proliferation |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|