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Intracellular Hormone Receptors01:08

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Lipid-soluble hormones diffuse across the plasma and nuclear membrane of target cells to bind to their specific intracellular receptors. These receptors act as transcription factors that regulate gene expression and protein synthesis in the target cell
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Transducer Mechanism: G Protein–Coupled Receptors01:30

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G Protein–Coupled Receptors (GPCRs) are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to various stimuli. GPCRs regulate critical physiological pathways and are excellent drug targets for treating diseases such as diabetes, cancer, obesity, depression, or Alzheimer's. Nearly 35% of approved drugs implement their therapeutic effects by selectively interacting with specific GPCRs.
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Water-soluble hormones cannot cross the plasma membrane, so they rely on protein receptors that span the membrane to trigger intracellular signaling pathways. These pathways then activate second messengers inside the cell, including cAMP or calcium ions.
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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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Insulin action is mediated through a receptor tyrosine kinase, akin to the IGF-1 receptor. The number of receptors per cell varies significantly, from 40 on erythrocytes to 300,000 on adipocytes and hepatocytes. The insulin receptor consists of linked α/β subunit dimers, forming a heterotetramer glycoprotein with two extracellular α subunits and two β subunits spanning the membrane. The α subunits inhibit the inherent tyrosine kinase activity of the β subunits, but...
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Endocrine Signaling01:45

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Endocrine cells produce hormones to communicate with remote target cells found in other organs. The hormone reaches these distant areas using the circulatory system. This exposes the whole organism to the hormone but only those cells expressing hormone receptors or target cells are affected. Thus, endocrine signaling induces slow responses from its target cells but these effects also last longer.
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Comparative Analysis of Human Growth Hormone in Serum Using SPRi, Nano-SPRi and ELISA Assays
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The growth hormone receptor.

Michael J Waters1

  • 1Institute for Molecular Bioscience, University of Queensland, St Lucia 4072, Australia.

Growth Hormone & IGF Research : Official Journal of the Growth Hormone Research Society and the International IGF Research Society
|June 11, 2015
PubMed
Summary

Growth hormone (GH) receptor activation involves hormone-induced receptor movements, separating Janus kinase 2 (JAK2) to initiate gene expression. This mechanism offers insights for developing cancer therapies.

Keywords:
JAK2MechanismReceptor structureSTAT5Src

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Area of Science:

  • Molecular Endocrinology
  • Cell Signaling
  • Receptor Biology

Background:

  • The growth hormone (GH) receptor, initially localized to specific tissues, is now recognized for its ubiquitous distribution, reflecting GH's diverse physiological roles.
  • GH influences metabolism, growth, cognition, immunity, and organ function primarily by altering gene expression via its membrane receptor.

Purpose of the Study:

  • To elucidate the molecular mechanism of GH receptor activation.
  • To understand the role of receptor-associated kinases, Janus kinase 2 (JAK2) and Src family kinases, in GH signaling.
  • To explore therapeutic implications of GH receptor signaling pathways.

Main Methods:

  • Investigated hormone-induced conformational changes in the GH receptor homodimer using biophysical techniques.
  • Analyzed the interaction between the GH receptor and associated JAK2 and Src kinases.
  • Examined downstream signaling events, including tyrosine phosphorylation and STAT5 activation.

Main Results:

  • GH binding induces specific movements within the receptor homodimer, including rotation and closer apposition above the cell membrane.
  • Hormone binding causes a conversion of transmembrane domains to a rotated crossover orientation, separating associated JAK2 molecules.
  • Separation of JAK2s releases inhibitory domains, enabling trans-activation and initiating downstream signaling cascades, including STAT5 phosphorylation.

Conclusions:

  • GH receptor activation is a dynamic process involving hormone-driven conformational changes and kinase dissociation.
  • This mechanism is crucial for mediating GH's pleiotropic effects, including gene expression regulation.
  • Understanding these signaling events provides a basis for developing targeted therapies, such as GH receptor antagonists for cancer treatment.