Accession Number : ADA320275

Title :   Breast Tumorigenesis: Interaction of Two Signaling Pathways--TGF--Beta Versus Estrogen Receptor.

Descriptive Note : Annual rept. 1 Sep 95-31 Aug 96,

Corporate Author : DUKE UNIV DURHAM NC

Personal Author(s) : Wang, Xiao-Fan ; Yingling, Jonathan

PDF Url : ADA320275

Report Date : OCT 1996

Pagination or Media Count : 14

Abstract : The Smad protein family has been genetically implicated in transforming growth factor BETA (TGF-BETA) like signaling pathways in Drosophila and Caenorhabditis elegans. To investigate the role of these proteins in mammalian signaling pathways, we have isolated and studied two murine Smads, Smad1 and Smad5. Using antibodies against Smad1 and Smad5, we show that these two Smads and an immunogenically related protein, presumably also a Smad, are phosphorylated in a time and dose dependent manner in response to TGF-BETA. Bone morphogenetic protein 2, a TGF-BETA superfamily ligand, induces phosphorylation of only the related Smad protein. Thus, TGF-BETA superfamily members may use overlapping yet distinct Smads to mediate their intracellular signals. Furthermore, transient overexpression of either Smad1 or Smad5 causes growth arrest, implicating the Smads in growth regulation. This work provides strong biochemical and preliminary functional evidence that Smad1 and Smad5 represent prototypic members of a family of mammalian proteins that may serve as mediators of signaling pathways for TGF-BETA superfamily members.

Descriptors :   *ESTROGENS, *BREAST CANCER, TRANSIENTS, RATS, HUMANS, BIOCHEMISTRY, PROTEINS, NEOPLASMS, SIGNALS, LIGANDS, ANTIBODIES, TRANSDUCERS, CELLS(BIOLOGY), SENSE ORGANS, MAMMARY GLANDS, GROWTH(PHYSIOLOGY), PHOSPHORYLATION, DROSOPHILA.

Subject Categories : Biochemistry
      Genetic Engineering and Molecular Biology
      Biology
      Medicine and Medical Research
      Organic Chemistry

Distribution Statement : APPROVED FOR PUBLIC RELEASE