Estrogen Regulates MAPK-Related Genes through Genomic and Nongenomic Interactions between IGF-I Receptor Tyrosine Kinase and Estrogen Receptor-Alpha Signaling Pathways in Human Uterine Leiomyoma Cells
Figure 6
Schematic illustration of genomic and nongenomic actions of on target gene transcription. Genomic actions involve the translocation of cytoplasmic E2-ER complexes to the nucleus which can then bind directly to estrogen response elements (EREs) in target gene promoters or nuclear E2-ER complexes. These complexes are tethered through protein-protein interactions to a transcription factor complex (TF) that contacts the target gene promoter to induce transcription of IGF-I and MAPK related genes. Nongenomically, E2 can bind to membrane associated ER which then binds to the adaptor protein, Src collagen homologue (Shc) to form a protein complex consisting of ER and Shc and/or ER and IGF-IR. E2 signals through the IGF-IR and activates MAPKp44/42, which can then phosphorylate ER at the serine118 site to initiate transcription (txn) of MAPK related genes. CCNDs = Cyclin Ds; MAPKs = mitogen-activated protein kinases; DLK1 = delta-like 1 homolog; COL1A1 = collagen type I alpha 1.
