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TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

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The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
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PI3K/mTOR/AKT Signaling Pathway01:22

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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...
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The JAK-STAT Signaling Pathway01:20

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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...
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Hedgehog Signaling Pathway02:33

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The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
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Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

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Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
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Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

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Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
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Related Experiment Video

Updated: Aug 12, 2025

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
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Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells

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The Stanniocalcin-PAPP-A-IGFBP-IGF Axis.

Claus Oxvig1, Cheryl A Conover2

  • 1Department of Molecular Biology and Genetics, Aarhus University, DK-8000 C, Aarhus, Denmark.

The Journal of Clinical Endocrinology and Metabolism
|January 31, 2023
PubMed
Summary
This summary is machine-generated.

Pappalysins (PAPP-A and PAPP-A2) regulate insulin-like growth factor (IGF) signaling by cleaving IGF binding proteins (IGFBPs). Stanniocalcins inhibit pappalysins, forming a complete IGF regulatory axis.

Keywords:
IGFIGF binding proteinIGFBPPAPP-ASTCinsulin-like growth factorpappalysinproteolysisproteolytic inhibitionstanniocalcin

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Endocrinology

Background:

  • Pappalysin metalloproteinases (PAPP-A, PAPP-A2) are key regulators of insulin-like growth factor (IGF) signaling.
  • They specifically cleave IGF binding proteins (IGFBPs), modulating IGF bioavailability and receptor interaction.
  • This proteolytic activity impacts both systemic and local IGF regulation in physiological and pathophysiological states.

Conclusions:

  • The stanniocalcin-PAPP-A-IGFBP-IGF axis is a crucial component of the IGF system.
  • Understanding the complex regulation, including multiple equilibria and inhibitory kinetics, is essential.
  • Further research is needed to integrate the non-IGF related functions of these regulatory proteins with IGF signaling.