TGF-beta receptor levels regulate the specificity of signaling pathway activation and biological effects of TGF-beta.

Publication Type:

Journal Article


Biochimica et biophysica acta, Volume 1793, Issue 7, p.1165-73 (2009)


2009, APOPTOSIS, Blotting, Western, Cells, Cultured, Center-Authored Paper, Clinical Research Division, Colonic Neoplasms, Cyclin-Dependent Kinase Inhibitor p21, Enzyme-Linked Immunosorbent Assay, Experimental Histopathology Core Facility, Extracellular Signal-Regulated MAP Kinases, Genomics Core Facility, Humans, Luciferases, MAP Kinase Signaling System, Phosphatidylinositol 3-Kinases, Protein-Serine-Threonine Kinases, Proto-Oncogene Proteins c-akt, Receptors, Transforming Growth Factor beta, Reverse Transcriptase Polymerase Chain Reaction, RNA, Messenger, Scientific Imaging Core Facility, Shared Resources, Signal Transduction, Smad7 Protein, Transforming Growth Factor beta


TGF-beta is a pluripotent cytokine that mediates its effects through a receptor composed of TGF-beta receptor type II (TGFBR2) and type I (TGFBR1). The TGF-beta receptor can regulate Smad and nonSmad signaling pathways, which then ultimately dictate TGF-beta's biological effects. We postulated that control of the level of TGFBR2 is a mechanism for regulating the specificity of TGF-beta signaling pathway activation and TGF-beta's biological effects. We used a precisely regulatable TGFBR2 expression system to assess the effects of TGFBR2 expression levels on signaling and TGF-beta mediated apoptosis. We found Smad signaling and MAPK-ERK signaling activation levels correlate directly with TGFBR2 expression levels. Furthermore, p21 levels and TGF-beta induced apoptosis appear to depend on relatively high TGFBR2 expression and on the activation of the MAPK-ERK and Smad pathways. Thus, control of TGFBR2 expression and the differential activation of TGF-beta signaling pathways appears to be a mechanism for regulating the specificity of the biological effects of TGF-beta.