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Smad-dependent and Smad-independent pathways in TGF-β family signalling

Naturevolume 425pages577584 (2003) | Download Citation

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Abstract

Transforming growth factor-β (TGF-β) proteins regulate cell function, and have key roles in development and carcinogenesis. The intracellular effectors of TGF-β signalling, the Smad proteins, are activated by receptors and translocate into the nucleus, where they regulate transcription. Although this pathway is inherently simple, combinatorial interactions in the heteromeric receptor and Smad complexes, receptor-interacting and Smad-interacting proteins, and cooperation with sequence-specific transcription factors allow substantial versatility and diversification of TGF-β family responses. Other signalling pathways further regulate Smad activation and function. In addition, TGF-β receptors activate Smad-independent pathways that not only regulate Smad signalling, but also allow Smad-independent TGF-β responses.

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We apologize to the many researchers whose work could not be cited because of space limitations or was only cited indirectly by referring to reviews or more recent papers.

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  1. Departments of Growth and Development, and Anatomy, Programs in Cell Biology and Developmental Biology, University of California at San Francisco, San Francisco, California, 94143-0640, USA

    • Rik Derynck
  2. Laboratory of Cellular and Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, 20892-4254, USA

    • Ying E. Zhang

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