Phospho-control of TGF-beta superfamily signaling.
Members of the transforming growth factor-beta (TGF-beta) family control a broad range of cellular responses in metazoan organisms via autocrine, paracrine, and endocrine modes. Thus, aberrant TGF-beta signaling can play a key role in the pathogenesis of several diseases, including cancer. TGF-beta signaling pathways are activated by a short phospho-cascade, from receptor phosphorylation to the subsequent phosphorylation and activation of downstream signal transducers called R-Smads. R-Smad phosphorylation state determines Smad complex assembly/disassembly, nuclear import/export, transcriptional activity and stability, and is thus the most critical event in TGF-beta signaling. Dephosphorylation of R-Smads by specific phosphatases prevents or terminates TGF-beta signaling, highlighting the need to consider Smad (de)phosphorylation as a tightly controlled and dynamic event. This article illustrates the essential roles of reversible phosphorylation in controlling the strength and duration of TGF-beta signaling and the ensuing physiological responses.
Wrighton
Katharine H
KH
Michael E. DeBakey Department of Surgery, Department of Molecular & Cellular Biology and Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA.
Lin
Xia
X
Feng
Xin-Hua
XH
D000818:Animals; D010766:Phosphorylation; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*; D015398:Signal Transduction; D051785:Smad Proteins / Q000502:physiology; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000502:physiology*; D025801:Ubiquitin / Q000378:metabolism
D018125:Receptors, Transforming Growth Factor beta; D051785:Smad Proteins; D016212:Transforming Growth Factor beta; D025801:Ubiquitin