Soluble mannose 6-phosphate/insulin-like growth factor II (IGF-II) receptor inhibits interleukin-6-type cytokine-dependent proliferation by neutralization of IGF-II
| Autor: | Frédéric Blanchard, Benjamin Chaigne-Delalande, Anne Godard, Patricia Vusio, Laurence Duplomb, Yannick Jacques, Sylvie Raher |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
STAT3 Transcription Factor
medicine.medical_specialty Cell Survival medicine.medical_treatment Mannose 6-phosphate CHO Cells Protein Serine-Threonine Kinases Antibodies Receptor IGF Type 2 chemistry.chemical_compound Insulin-like growth factor Mice Endocrinology Antigens CD Insulin-Like Growth Factor II Internal medicine Cell Line Tumor Cricetinae Proto-Oncogene Proteins medicine Cytokine Receptor gp130 Animals Humans Receptor Protein kinase B Membrane Glycoproteins biology Cell growth Interleukin-6 Interleukin-11 DNA-Binding Proteins Cytokine chemistry Solubility Insulin-like growth factor 2 biology.protein Trans-Activators Mitogen-Activated Protein Kinases Leukemia inhibitory factor Proto-Oncogene Proteins c-akt Cell Division Signal Transduction |
| Zdroj: | Endocrinology. 144(12) |
| ISSN: | 0013-7227 |
| Popis: | The calcium-independent mannose 6-phosphate receptor (CIMPR) is a receptor for multiple ligands, including leukemia inhibitory factor (LIF), an IL-6 type cytokine, and IGF-II. CIMPR targets newly synthesized ligands to lysosomes and induces internalization/degradation of secreted ligands. A natural soluble form of CIMPR (sCIMPR) neutralizes IGF-II mitogenic potency on hepatocytes and fibroblasts. Herein we show that sCIMPR also inhibits LIF-driven proliferation of myeloid and lymphoid cell lines. Similar inhibition was observed with IL-6 and IL-11, two other IL-6-type cytokines that do not interact with CIMPR. Neutralizing anti-IGF-II antibodies inhibited IL-6-, IL-11-, and LIF-driven cell proliferation to the same extent as sCIMPR, suggesting that neutralization of serum IGF-II by sCIMPR plays a major role in IL-6-type cytokine-dependent cell proliferation. Confirming this idea, ERK1/2 and AKT/protein kinase B, the kinases necessary for cell proliferation and survival, were activated by IGF-II alone or by the association of IL-6-type cytokines and IGF-II. IL-6-type cytokines alone (up to 10 ng/ml) did not activate ERK1/2 or AKT, but did activate STAT3 (signal transducer and activator of transcription 3), a transcription factor necessary for the G1 to S phase cell cycle transition. Activation of ERK1/2 and AKT by IGF-II thus appears essential to sustain cellular expansion driven by IL-6-type cytokines. |
| Databáze: | OpenAIRE |
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