title: Examining Crosstalk among Transforming Growth Factor β, Bone Morphogenetic Protein, and Wnt Pathways.
abstract: The integration of morphogenic signals by cells is not well understood. A growing body of literature suggests increasingly complex coupling among classically defined pathways. Given this apparent complexity, it is difficult to predict where, when, or even whether crosstalk occurs. Here, we investigated pairs of morphogenic pathways, previously reported to have multiple points of crosstalk, which either do not share (TGFβ and Wnt/β-catenin) or share (TGFβ and bone morphogenetic protein (BMP)) core signaling components. Crosstalk was measured by the ability of one morphogenic pathway to cross-activate core transcription factors and/or target genes of another morphogenic pathway. In contrast to previous studies, we found a surprising absence of crosstalk between TGFβ and Wnt/β-catenin. Further, we did not observe expected cross-pathway inhibition in between TGFβ and BMP, despite the fact that both use (or could compete) for the shared component SMAD4. Critical to our assays was a separation of timescales, which helped separate crosstalk due to initial signal transduction from subsequent post-transcriptional feedback events. Our study revealed fewer (and different) inter-morphogenic pathway crosstalk connections than expected; even pathways that share components can be insulated from one another.
authors.affiliation: From the Green Center for Systems Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390 and.
authors.forename: Adam D
authors.initials: AD
authors.lastname: Coster
authors.affiliation: From the Green Center for Systems Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390 and.
authors.forename: Curtis A
authors.initials: CA
authors.lastname: Thorne
authors.affiliation: From the Green Center for Systems Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390 and Lani.Wu@ucsf.edu.|the Department of Pharmaceutical Chemistry, University of California, San Francisco, California 94158.
authors.forename: Lani F
authors.initials: LF
authors.lastname: Wu
authors.affiliation: From the Green Center for Systems Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390 and Steven.Altschuler@ucsf.edu.|the Department of Pharmaceutical Chemistry, University of California, San Francisco, California 94158.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Altschuler
mesh_terms: D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D019573:Epithelium, Corneal / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D051153:Wnt Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D019485:Bone Morphogenetic Proteins; D016212:Transforming Growth Factor beta; D051153:Wnt Proteins; D051176:beta Catenin
keywords: Wnt signaling; bone morphogenetic protein (BMP); imaging; signal transduction; transcription factor; transforming growth factor β (TGF-β)