SMADs: mediators and regulators of TGF-β signaling

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Abstract

The discovery of SMAD proteins has allowed the delineation of a mechanism by which TGF-β and related growth factors convey their signals from membrane receptors all the way into the nucleus. SMADs are directly phosphorylated and activated by the receptors and then form heteromeric SMAD-SMAD complexes that move into the nucleus where they orchestrate transcriptional responses. In rapid succession, recent reports have identified different modes of SMAD regulation by phosphorylation and have defined the SMAD domains that mediate SMAD interactions, binding to DNA or transcriptional activation. The recent discovery of antagonistic SMADs and regulatory crosstalk with Ras/MAP-kinase pathways add to our rapidly expanding understanding of this major regulatory network.

References (52)

  • AB Roberts et al.
  • BLM Hogan

    Bone morphogenetic proteins: multifunctional regulators of vertebrate development

    Genes Dev

    (1996)
  • J Massagué et al.
  • LA Raftery et al.

    Genetic screens to identify elements of the decapentaplegic signaling pathway in Drosophila

    Genetics

    (1995)
  • JJ Sekelsky et al.

    Genetic characterization and cloning of Mothers against dpp, a gene required for decapentaplegic function in Drosophila melanogaster

    Genetics

    (1995)
  • JM Yingling et al.

    Mammalian Dwarfins are phosphorylated in response to TGF-β and are implicated in control of cell growth

    Proc Natl Acad Sci USA

    (1996)
  • F Liu et al.

    A human Mad protein acting as a BMP-regulated transcriptional activator

    Nature

    (1996)
  • M Kretzschmar et al.

    The TGF-β family mediator Smad1 is phosphorylated directly and activated functionally by the BMP receptor kinase

    Genes Dev

    (1997)
  • PA Hoodless et al.

    MADR1, a MAD-related protein that functions in BMP2 signalling pathways

    Cell

    (1996)
  • V Wiersdorff et al.

    Mad acts downstream of Dpp receptors, revealing differential requirement for dpp signaling in initiation and propagation of morphogenesis in the Drosophila eye

    Development

    (1996)
  • C Savage et al.

    Caenorhabditis elegans genes sma-2, sma-3 and sma-4 define a conserved family of transforming growth factor β pathway components

    Proc Natl Acad Sci USA

    (1996)
  • Y Zhang et al.

    Receptor-associated Mad homologues synergize as effectors of the TGFβ response

    Nature

    (1996)
  • M Macias-Silva et al.

    MADR2 is a substrate of the TGFβ receptor and phosphorylation is required for nuclear accumulation and signaling

    Cell

    (1996)
  • K Eppert et al.

    MADR2 maps to 18q21 and encodes a TGFβ-regulated MAD-related protein that is functionally mutated in colorectal carcinoma

    Cell

    (1996)
  • A Nakao et al.

    Identification of Smad2, a human Mad-related protein in the transforming growth factor-β signaling pathway

    J Biol Chem

    (1997)
  • SA Hahn et al.

    DPC4, a candidate tumor suppressor gene at human chromosome 18q21.1

    Science

    (1996)

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