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Phosphoinositides and PIPs01:42

Phosphoinositides and PIPs

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Phosphoinositides are a group of phospholipids containing a glycerol backbone with two fatty acid chains and a phosphate attached to a myoinositol sugar ring. The inositol head group extends into the cytoplasm, where it is modified by adding phosphate groups to form phosphatidylinositol phosphates or PIPs.
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Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
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  6. Phosphoproteomics Reveals Selective Regulation Of Signaling Pathways By Lysophosphatidic Acid Species In Macrophages

Phosphoproteomics Reveals Selective Regulation of Signaling Pathways by Lysophosphatidic Acid Species in Macrophages

Raimund Dietze1, Witold Szymanski2,3, Kaire Ojasalu1

  • 1Department of Translational Oncology, Center for Tumor Biology and Immunology, Philipps University, 35043 Marburg, Germany.

Cells
|May 24, 2024

Related Experiment Videos

Proteomic Analysis of Human Macrophage Polarization Under a Low Oxygen Environment
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Proteomic Analysis of Human Macrophage Polarization Under a Low Oxygen Environment

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Proteomic Profiling of Macrophages by 2D Electrophoresis

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Fluorescence-Based Measurements of Phosphatidylserine/Phosphatidylinositol 4-Phosphate Exchange Between Membranes
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Fluorescence-Based Measurements of Phosphatidylserine/Phosphatidylinositol 4-Phosphate Exchange Between Membranes

Published on: March 14, 2021

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View abstract on PubMed

Summary
This summary is machine-generated.

Lysophosphatidic acid (LPA) species differentially regulate macrophages in the tumor microenvironment. Specific LPA types, like 20:4 LPA, enhance macrophage migration and survival, potentially promoting cancer progression.

Area of Science:

  • Oncology
  • Immunology
  • Biochemistry

Background:

  • Lysophosphatidic acid (LPA) is prevalent in the tumor microenvironment (TME) and impacts cancer progression.
  • Specific LPA species (18:0 and 20:4) correlate with poor outcomes in ovarian cancer.
  • The effect of LPA on macrophages within the TME is not well understood.

Purpose of the Study:

  • To investigate the distinct effects of different LPA species on human monocyte-derived macrophages.
  • To identify signaling pathways and cellular functions modulated by specific LPA species in macrophages.

Main Methods:

  • Unbiased phosphoproteomics to analyze global protein phosphorylation changes.
  • RNA sequencing to profile gene expression.
  • Assessment of actin cytoskeleton dynamics and cell migration.
Keywords:
RHO/RAC1 signalingcholesterol biosynthesislysophosphatidic acidmacrophages

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Proteomic Analysis of Human Macrophage Polarization Under a Low Oxygen Environment
10:15

Proteomic Analysis of Human Macrophage Polarization Under a Low Oxygen Environment

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Proteomic Profiling of Macrophages by 2D Electrophoresis
07:53

Proteomic Profiling of Macrophages by 2D Electrophoresis

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08:49

Fluorescence-Based Measurements of Phosphatidylserine/Phosphatidylinositol 4-Phosphate Exchange Between Membranes

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Main Results:

  • Distinct LPA species (18:0 vs. 20:4) induce unique phosphoproteomic signatures in macrophages, with significant differences in upregulated and downregulated phosphosites.
  • RHO/RAC1 GTPase signaling is a key pathway affected by LPA, influencing the actin cytoskeleton and macrophage migration.
  • 20:4 LPA specifically activates p38 signaling and modulates genes involved in cholesterol/lipid metabolism, while 18:0 LPA shows a different pattern for AKT activation.

Conclusions:

  • LPA species exert distinct, species-specific effects on macrophage signaling and function.
  • These differential effects, including enhanced migration and survival pathways, suggest a role for specific LPA species in promoting pro-tumorigenic macrophage functions within the TME.
phosphoproteomics