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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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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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Filopodia are thin, actin-rich cellular protrusions that play an important role in many fundamental cellular functions. They vary in their occurrence, length, and positioning in different cell types, suggesting their diverse roles.
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Actin is a family of globular proteins that are highly abundant in eukaryotic cells. It makes up approximately 1-5% of total cell protein concentration. Actin monomers polymerize to form a complex network of polarized filaments, the actin cytoskeleton, that plays a crucial role in many cellular processes, including cell motility, division, endocytosis, and metastasis of cancer cells.
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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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Aip1p Dynamics Are Altered by the R256H Mutation in Actin
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Dysregulated actin dynamics in activated PI3Kδ syndrome.

Jacqueline G Wallace1, Pedro Zambrano-Rodas2, Wilmer Córdova-Calderón3

  • 1Division of Immunology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.

Clinical Immunology (Orlando, Fla.)
|November 25, 2019
PubMed
Summary

Activated PI3Kδ syndrome (APDS) involves PIK3CD mutations. This study found abnormal actin dynamics and increased apoptosis in APDS cells, suggesting a link between actin impairment and the disease.

Area of Science:

  • Immunology
  • Cell Biology
  • Genetics

Background:

  • Activated PI3Kδ syndrome (APDS) Type I is caused by PIK3CD gain-of-function mutations.
Keywords:
APDSActinPI3Kδ

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  • Lymphopenia in APDS is hypothesized to involve abnormal actin dynamics, but this has not been directly studied in patients.
  • A patient with APDS presented with necrotic skin lesions responsive to immunosuppression.