Related Experiment Video

Updated: Aug 13, 2026

Detection of Signaling Effector-Complexes Downstream of BMP4 Using in situ PLA, a Proximity Ligation Assay
12:52

Detection of Signaling Effector-Complexes Downstream of BMP4 Using in situ PLA, a Proximity Ligation Assay

Published on: March 4, 2011

Bridging the BMP and Wnt pathways by PI3 kinase/Akt and 14-3-3zeta

Qiang Tian1, Xi C He, Leroy Hood

  • 1Institute for Systems Biology, Seattle, Washington 98103, USA. qtian@systemsbiology.org

Cell Cycle (Georgetown, Tex.)
|January 19, 2005
PubMed

Insights

Inactivating Bone Morphogenetic Protein (BMP) signaling in mice leads to intestinal polyps by boosting Wnt/beta-catenin signaling and activating Akt in intestinal stem cells (ISCs). 14-3-3zeta protein further enhances this activation.

Area of Science:

  • Gastroenterology
  • Developmental Biology
  • Molecular Biology

Background:

  • The Bone Morphogenetic Protein (BMP), PTEN, and Wnt/beta-catenin signaling pathways are crucial for normal intestinal development and regeneration.
  • Aberrant activation or inactivation of these pathways can lead to intestinal polyposis.

Purpose of the Study:

  • To investigate the role of BMP signaling inactivation in intestinal polyposis.
  • To elucidate the molecular mechanisms linking BMP signaling to Wnt/beta-catenin and PI3K/Akt pathways in intestinal stem cells (ISCs).

Main Methods:

  • Genetic targeting of BMPR1A in mice to inactivate BMP signaling.
  • Proteomic analysis of the beta-catenin complex.
  • Analysis of signaling pathway activation in intestinal cells, particularly ISCs.

Main Results:

  • Inactivation of BMP signaling in mice resulted in multiple intestinal polyps.
  • BMP signaling loss led to increased crypts and stem cells, with enhanced Wnt signaling.
  • Beta-catenin activation and PTEN inactivation, leading to Akt activation, were predominantly observed in ISCs.
  • Proteomic analysis identified 14-3-3zeta in the beta-catenin complex, facilitating Akt-mediated activation.

Conclusions:

  • BMP signaling normally suppresses ISC self-renewal by inhibiting Wnt/beta-catenin signaling.
  • The PTEN/Akt pathway and 14-3-3zeta protein mediate cross-talk between BMP and Wnt/beta-catenin signaling in ISCs.
  • This interaction is critical for regulating intestinal stem cell behavior and preventing polyposis.

More Related Videos

Site-Directed Immobilization of Bone Morphogenetic Protein 2 to Solid Surfaces by Click Chemistry11:20

Site-Directed Immobilization of Bone Morphogenetic Protein 2 to Solid Surfaces by Click Chemistry

Published on: March 29, 2018

Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway07:15

Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway

Published on: August 23, 2024

Related Concept Videos

Canonical Wnt Signaling Pathway02:54

Canonical Wnt Signaling Pathway

The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which results in tumor...
Non-Canonical Wnt Signaling Pathways01:41

Non-Canonical Wnt Signaling Pathways

Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
Non-Canonical Wnt Signaling Pathways01:41

Non-Canonical Wnt Signaling Pathways

Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...