Signal transduction pathways induced by heregulin in MDA-MB-453 breast cancer cells
| Autor: | L, Sepp-Lorenzino, I, Eberhard, Z, Ma, C, Cho, H, Serve, F, Liu, N, Rosen, R, Lupu |
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| Rok vydání: | 1996 |
| Předmět: |
Receptor
ErbB-4 Receptor ErbB-3 Transcription Genetic Neuregulin-1 Molecular Sequence Data Breast Neoplasms Protein Serine-Threonine Kinases src Homology Domains Mitogen-Activated Protein Kinase 10 Proto-Oncogene Proteins Tumor Cells Cultured Humans Amino Acid Sequence Phosphorylation Promoter Regions Genetic 1-Phosphatidylinositol 4-Kinase Glycoproteins Genes fos Protein-Tyrosine Kinases ErbB Receptors Gene Expression Regulation Neoplastic Phosphotransferases (Alcohol Group Acceptor) Tyrosine Female Mitogen-Activated Protein Kinases Carrier Proteins Protein Binding Signal Transduction |
| Zdroj: | Oncogene. 12(8) |
| ISSN: | 0950-9232 |
| Popis: | Heregulins (HRGs) induce tyrosine phosphorylation of several members of the erb-B family of receptors. Although originally isolated as the ligands for p185c-erb-2, recent evidence suggests that other receptors of the erbB family, including p180erbB-3 and p180erbB-4, are their true cognate receptors. Stimulation of MDA MB-453 cells with HRG beta 2 resulted in the tyrosine phosphorylation of p185c-erbB-2 and p180erbB-4 in a time- and dose-dependent fashion. This event was accompanied by the formation of multimeric complexes between the activated receptors and SH2-containing proteins. Ligand caused p120-rasGTPase activating protein (GAP), SHC and the p85 subunit of phosphatidylinositol-3'-kinase (PI3K) to be associated with both p185c-erbB-2 and p180erbB-4. In addition, tyrosine phosphorylation of p85-PI3K and SHC, but not of GAP or of its associated p62 and p190 proteins, was also detected. HRG also induced the association of GRB2 with tyrosine phosphorylated p185c-erbB-2, p180erbB-4 and SHC. Activation of mitogen-activated protein kinase (MAPK) (30-fold over untreated controls) was observed upon receptor(s) activation, as it was the induction of the immediate early gene c-fos (200-fold). These observations suggest that p21ras activation plays a role in the HRG pathway. Furthermore, comparative analysis of the binding of p85-PI3K to 185c-erbB-2 and p180erbB-4, revealed a preferential association with activated p180erbB-4. These findings might suggest a model of HRG action in which the relative expression of the various erb-B family members and the partitioning of signal transduction molecules between each type of receptor might determine the nature of the signal elicited by the ligand and the biological response attained. |
| Databáze: | OpenAIRE |
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