Activated type I TGFbeta receptor (Alk5) kinase confers enhancedsurvival to mammary epithelial cells and accelerates mammary tumorprogression Metadata

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Title

  • Main Title Activated type I TGFbeta receptor (Alk5) kinase confers enhancedsurvival to mammary epithelial cells and accelerates mammary tumorprogression

Creator

  • Author: Muraoka-Cook, Rebecca S.
    Creator Type: Personal
  • Author: Shin, Incheol
    Creator Type: Personal
  • Author: Yi, Jae Youn
    Creator Type: Personal
  • Author: Easterly,Evangeline
    Creator Type: Personal
  • Author: Barcellos-Hoff, Mary Helen
    Creator Type: Personal
  • Author: Yingling, Jonathan M.
    Creator Type: Personal
  • Author: Zent, Roy
    Creator Type: Personal
  • Author: Arteaga, Carlos L.
    Creator Type: Personal

Contributor

  • Sponsor: United States. Department of Energy.
    Contributor Type: Organization
  • Sponsor: National Institute of Health Grant R01 CA62212 andCA80195 and AG022413, Breast Cancer Specialized Program of ResearchExcellence Grant P50 CA98131, Vanderbilt-Ingram Comprehensive CancerCenter Support Grant P30 CA68485
    Contributor Type: Organization

Publisher

  • Name: Lawrence Berkeley National Laboratory
    Place of Publication: Berkeley, California
    Additional Info: Ernest Orlando Lawrence Berkeley National Laboratory, Berkeley, CA (United States)

Date

  • Creation: 2005-01-02

Language

  • English

Description

  • Content Description: The transforming growth factor-betas (TGF{beta}s) are members of a large superfamily of pleiotropic cytokines that also includes the activins and the bone morphogenetic proteins (BMPs). Members of the TGF{beta} family regulate complex physiological processes such cell proliferation, differentiation, adhesion, cell-cell and cell-matrix interactions, motility, and cell death, among others (Massague, 1998). Dysregulation of TGF{beta} signaling contributes to several pathological processes including cancer, fibrosis, and auto-immune disorders (Massague et al., 2000). The TGF{beta}s elicit their biological effects by binding to type II and type I transmembrane receptor serine-threonine kinases (T{beta}RII and T{beta}RI) which, in turn, phosphorylated Smad 2 and Smad 3. Phosphorylated Smad 2/3 associate with Smad 4 and, as a heteromeric complex, translocate to the nucleus where they regulate gene transcription. The inhibitory Smad7 down regulates TGF{beta} signaling by binding to activated T{beta}RI and interfering with its ability to phosphorylate Smad 2/3 (Derynck and Zhang, 2003; Shi and Massague, 2003). Signaling is also regulated by Smad proteolysis. TGF{beta} receptor-mediated activation results in multi-ubiquitination of Smad 2 in the nucleus and subsequent degradation of Smad 2 by the proteasome (Lo and Massague, 1999). Activation of TGF{beta} receptors also induces mobilization of a Smad 7-Smurf complex from the nucleus to the cytoplasm; this complex recognizes the activated receptors and mediates their ubiquitination and internalization via caveolin-rich vesicles, leading to termination of TGF{beta} signaling (Di Guglielmo et al., 2003). Other signal transducers/pathways have been implicated in TGF{beta} actions. These include the extracellular signal-regulated kinase (Erk), c-Jun N-terminal kinase (Jnk), p38 mitogen-activated protein kinase (MAPK), protein phosphatase PP2A, phosphatidylinositol-3 kinase (PI3K), and the family of Rho GTPases [reviewed in (Derynck and Zhang, 2003)]. Although signaling by Smads has been shown to be causally associated with the anti-proliferative effect of TGF{beta} (Datto et al., 1999; Liu et al., 1997), the role of non-Smad effectors on mediating the cellular effects of TGF{beta} is less well characterized.

Subject

  • Keyword: Death
  • Keyword: Neoplasms
  • Keyword: Transcription
  • Keyword: Genes
  • Keyword: Cell Proliferation
  • Keyword: Cytoplasm
  • STI Subject Categories: 59 Basic Biological Sciences
  • Keyword: Phosphotransferases
  • Keyword: Proteins
  • Keyword: Adhesion
  • Keyword: Lymphokines
  • Keyword: Phosphatases
  • Keyword: Fibrosis
  • Keyword: Proteolysis
  • Keyword: Biological Effects

Source

  • Journal Name: Oncogene; Journal Volume: none; Related Information: Journal Publication Date: Sept. 26,2005

Collection

  • Name: Office of Scientific & Technical Information Technical Reports
    Code: OSTI

Institution

  • Name: UNT Libraries Government Documents Department
    Code: UNTGD

Resource Type

  • Article

Format

  • Text

Identifier

  • Report No.: LBNL--55195
  • Grant Number: DE-AC02-05CH11231
  • Office of Scientific & Technical Information Report Number: 860960
  • Archival Resource Key: ark:/67531/metadc782778