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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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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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The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
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When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze...
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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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Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the  phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and...
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SorLA and CLC:CLF-1-dependent Downregulation of CNTFR&#945; as Demonstrated by Western Blotting, Inhibition of Lysosomal Enzymes, and Immunocytochemistry
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Understanding LAG-3 Signaling.

Luisa Chocarro1, Ester Blanco1, Miren Zuazo1

  • 1Oncoimmunology Group, Navarrabiomed-Public University of Navarre, IdISNA, 31008 Pamplona, Navarra, Spain.

International Journal of Molecular Sciences
|June 2, 2021
PubMed
Summary
This summary is machine-generated.

Lymphocyte activation gene 3 (LAG-3) is an immune checkpoint target for cancer immunotherapy. Understanding LAG-3 signaling is crucial for developing next-generation cancer treatments, despite its poorly understood mechanisms compared to PD-1 and CTLA-4.

Keywords:
LAG-3cancer signalingimmune checkpointimmunotherapytargeted therapy

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Area of Science:

  • Immunology
  • Cancer Biology
  • Molecular Biology

Background:

  • Lymphocyte activation gene 3 (LAG-3) is an inhibitory immune checkpoint receptor.
  • LAG-3 regulates T cell activation and effector functions, playing a key role in immune responses.
  • It is considered a promising target for anti-cancer immunotherapies, similar to PD-1 and CTLA-4.

Purpose of the Study:

  • To summarize the current understanding of LAG-3 signaling.
  • To elucidate the mechanisms of action of LAG-3.
  • To discuss the clinical applications of LAG-3 in cancer therapy.

Main Methods:

  • Review of current literature on LAG-3 signaling pathways.
  • Analysis of non-conventional signaling motifs in LAG-3's intracellular domain.
  • Comparison of LAG-3's mechanisms with other immune checkpoint molecules like PD-1 and CTLA-4.

Main Results:

  • LAG-3 exhibits inhibitory activities comparable to PD-1 and CTLA-4.
  • Its precise mechanisms of action and relationship with other checkpoints are not fully understood.
  • Non-conventional signaling motifs contribute to LAG-3's inhibitory functions.

Conclusions:

  • LAG-3 is a significant target for next-generation cancer immunotherapies.
  • Further research into LAG-3 signaling mechanisms is essential for optimizing its clinical use.
  • Understanding LAG-3 is critical for advancing anti-cancer immune responses.