Lysophosphatidic acid: mitogen and motility factor

2003 ◽  
Vol 31 (6) ◽  
pp. 1209-1212 ◽  
Author(s):  
F.N. van Leeuwen ◽  
B.N.G. Giepmans ◽  
L.A. van Meeteren ◽  
W.H. Moolenaar
Keyword(s):  
G Proteins ◽  
Lysophosphatidic Acid ◽  
Recent Progress ◽  
Small Gtpases ◽  
G Protein Coupled Receptors ◽  
Signal Transduction Pathways ◽  
Potent Inducer ◽  
Motility Factor ◽  
Lpa Receptors ◽  
G Protein Coupled

LPA (lysophosphatidic acid), the simplest of al glycerophospholipids, is a potent inducer of cell proliferation, migration and survival. It does so by activating its cognate G-protein-coupled receptors, four of which have been identified. LPA receptors couple to at least three distinct G-proteins and thereby activate multiple signal transduction pathways, particularly those initiated by the small GTPases Ras, Rho and Rac. Our recent work has shown that LPA signals Rac activation via the Tiam1 GDP/GTP exchange factor and thereby stimulates cell migration. Here we discuss recent progress in our understanding of LPA action.

scholarly journals Autotaxin, a Secreted Lysophospholipase D, Is Essential for Blood Vessel Formation during Development

2006 ◽  
Vol 26 (13) ◽  
pp. 5015-5022 ◽  
Author(s):  
Laurens A. van Meeteren ◽  
Paula Ruurs ◽  
Catelijne Stortelers ◽  
Peter Bouwman ◽  
Marga A. van Rooijen ◽  
...  
Keyword(s):  
Lysophosphatidic Acid ◽  
Critical Role ◽  
G Protein Coupled Receptors ◽  
Blood Vessel Formation ◽  
Lysophospholipase D ◽  
Motility Factor ◽  
Nucleotide Pyrophosphatase ◽  
G Protein Coupled ◽  
Deficient Mice

ABSTRACT Autotaxin (ATX), or nucleotide pyrophosphatase-phosphodiesterase 2, is a secreted lysophospholipase D that promotes cell migration, metastasis, and angiogenesis. ATX generates lysophosphatidic acid (LPA), a lipid mitogen and motility factor that acts on several G protein-coupled receptors. Here we report that ATX-deficient mice die at embryonic day 9.5 (E9.5) with profound vascular defects in yolk sac and embryo resembling the Gα13 knockout phenotype. Furthermore, at E8.5, ATX-deficient embryos showed allantois malformation, neural tube defects, and asymmetric headfolds. The onset of these abnormalities coincided with increased expression of ATX and LPA receptors in normal embryos. ATX heterozygous mice appear healthy but show half-normal ATX activity and plasma LPA levels. Our results reveal a critical role for ATX in vascular development, indicate that ATX is the major LPA-producing enzyme in vivo, and suggest that the vascular defects in ATX-deficient embryos may be explained by loss of LPA signaling through Gα13.

scholarly journals Lysophosphatidic acids, cyclic phosphatidic acids and autotaxin as promising targets in therapies of cancer and other diseases.

2008 ◽  
Vol 55 (2) ◽  
pp. 227-240 ◽  
Author(s):  
Edyta Gendaszewska-Darmach
Keyword(s):  
Tumor Cell ◽  
G Protein Coupled Receptors ◽  
Autocrine Motility Factor ◽  
Motility Factor ◽  
Cellular Processes ◽  
Naturally Occurring ◽  
Lpa Receptors ◽  
Metastasis Research ◽  
Phosphatidic Acids ◽  
G Protein Coupled

Lysophospholipids have long been recognized as membrane phospholipid metabolites, but only recently lysophosphatidic acids (LPA) have been demonstrated to act on specific G protein-coupled receptors. The widespread expression of LPA receptors and coupling to several classes of G proteins allow LPA-dependent regulation of numerous processes, such as vascular development, neurogenesis, wound healing, immunity, and cancerogenesis. Lysophosphatidic acids have been found to induce many of the hallmarks of cancer including cellular processes such as proliferation, survival, migration, invasion, and neovascularization. Furthermore, autotaxin (ATX), the main enzyme converting lysophosphatidylcholine into LPA was identified as a tumor cell autocrine motility factor. On the other hand, cyclic phosphatidic acids (naturally occurring analogs of LPA generated by ATX) have anti-proliferative activity and inhibit tumor cell invasion and metastasis. Research achievements of the past decade suggest implementation of preclinical and clinical evaluation of LPA and its analogs, LPA receptors, as well as autotaxin as potential therapeutic targets.

scholarly journals Autotaxin-Lysophosphatidic Acid: From Inflammation to Cancer Development

2017 ◽  
Vol 2017 ◽  
pp. 1-15 ◽  
Author(s):  
Silvia Anahi Valdés-Rives ◽  
Aliesha González-Arenas
Keyword(s):  
Wound Healing ◽  
G Protein ◽  
Cancer Progression ◽  
Lysophosphatidic Acid ◽  
Therapeutic Target ◽  
G Protein Coupled Receptors ◽  
Cancer Development ◽  
Cellular Processes ◽  
Lpa Receptors ◽  
G Protein Coupled

Lysophosphatidic acid (LPA) is a ubiquitous lysophospholipid and one of the main membrane-derived lipid signaling molecules. LPA acts as an autocrine/paracrine messenger through at least six G protein-coupled receptors (GPCRs), known as LPA1–6, to induce various cellular processes including wound healing, differentiation, proliferation, migration, and survival. LPA receptors and autotaxin (ATX), a secreted phosphodiesterase that produces this phospholipid, are overexpressed in many cancers and impact several features of the disease, including cancer-related inflammation, development, and progression. Many ongoing studies aim to understand ATX-LPA axis signaling in cancer and its potential as a therapeutic target. In this review, we discuss the evidence linking LPA signaling to cancer-related inflammation and its impact on cancer progression.

scholarly journals Signaling from G Protein-coupled Receptors to ERK5/Big MAPK 1 Involves Gαqand Gα12/13Families of Heterotrimeric G Proteins

2000 ◽  
Vol 275 (28) ◽  
pp. 21730-21736 ◽  
Author(s):  
Shigetomo Fukuhara ◽  
Maria Julia Marinissen ◽  
Mario Chiariello ◽  
J. Silvio Gutkind
Keyword(s):  
G Protein ◽  
G Proteins ◽  
G Protein Coupled Receptors ◽  
Heterotrimeric G Proteins ◽  
G Protein Coupled

scholarly journals Physiology of the orexinergic/hypocretinergic system: a revisit in 2012

2013 ◽  
Vol 304 (1) ◽  
pp. C2-C32 ◽  
Author(s):  
Jyrki P. Kukkonen
Keyword(s):  
Central Nervous System ◽  
G Proteins ◽  
Cellular Responses ◽  
G Protein Coupled Receptors ◽  
Heterotrimeric G Proteins ◽  
Neuronal Excitation ◽  
System A ◽  
The Central Nervous System ◽  
G Protein Coupled ◽  
Systemic Responses

The neuropeptides orexins and their G protein-coupled receptors, OX1and OX2, were discovered in 1998, and since then, their role has been investigated in many functions mediated by the central nervous system, including sleep and wakefulness, appetite/metabolism, stress response, reward/addiction, and analgesia. Orexins also have peripheral actions of less clear physiological significance still. Cellular responses to the orexin receptor activity are highly diverse. The receptors couple to at least three families of heterotrimeric G proteins and other proteins that ultimately regulate entities such as phospholipases and kinases, which impact on neuronal excitation, synaptic plasticity, and cell death. This article is a 10-year update of my previous review on the physiology of the orexinergic/hypocretinergic system. I seek to provide a comprehensive update of orexin physiology that spans from the molecular players in orexin receptor signaling to the systemic responses yet emphasizing the cellular physiological aspects of this system.

scholarly journals A2B Adenosine Receptor and Cancer

2019 ◽  
Vol 20 (20) ◽  
pp. 5139 ◽  
Author(s):  
Zhan-Guo Gao ◽  
Kenneth A. Jacobson
Keyword(s):  
G Proteins ◽  
Anticancer Agents ◽  
Immune Suppression ◽  
Adenosine Receptors ◽  
Immune Surveillance ◽  
G Protein Coupled Receptors ◽  
Normal Tissues ◽  
Cancer Tissues ◽  
G Protein Coupled

There are four subtypes of adenosine receptors (ARs), named A1, A2A, A2B and A3, all of which are G protein-coupled receptors (GPCRs). Locally produced adenosine is a suppressant in anti-tumor immune surveillance. The A2BAR, coupled to both Gαs and Gαi G proteins, is one of the several GPCRs that are expressed in a significantly higher level in certain cancer tissues, in comparison to adjacent normal tissues. There is growing evidence that the A2BAR plays an important role in tumor cell proliferation, angiogenesis, metastasis, and immune suppression. Thus, A2BAR antagonists are novel, potentially attractive anticancer agents. Several antagonists targeting A2BAR are currently in clinical trials for various types of cancers. In this review, we first describe the signaling, agonists, and antagonists of the A2BAR. We further discuss the role of the A2BAR in the progression of various cancers, and the rationale of using A2BAR antagonists in cancer therapy.

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