Lysophospholipids in the limelight

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Lysophosphatidic acid (LPA) is a serum phospholipid that evokes growth factor–like responses in many cell types through the activation of its G protein–coupled receptors. Although much is known about LPA signaling, it has remained unclear where and how bioactive LPA is produced. Umezu-Goto et al. (2002)(this issue, page 227) have purified a serum lysophospholipase D that generates LPA from lysophosphatidylcholine and found it to be identical to autotaxin, a cell motility–stimulating ectophosphodiesterase implicated in tumor progression. This result is surprising, as there was previously no indication that autotaxin could act as a phospholipase.

Related collections

Most cited references 18

Record: found
Abstract: found
Article: not found

Rho GTPases Control Polarity, Protrusion, and Adhesion during Cell Movement

Catherine Nobes, Alan Hall (1999)

Cell movement is essential during embryogenesis to establish tissue patterns and to drive morphogenetic pathways and in the adult for tissue repair and to direct cells to sites of infection. Animal cells move by crawling and the driving force is derived primarily from the coordinated assembly and disassembly of actin filaments. The small GTPases, Rho, Rac, and Cdc42, regulate the organization of actin filaments and we have analyzed their contributions to the movement of primary embryo fibroblasts in an in vitro wound healing assay. Rac is essential for the protrusion of lamellipodia and for forward movement. Cdc42 is required to maintain cell polarity, which includes the localization of lamellipodial activity to the leading edge and the reorientation of the Golgi apparatus in the direction of movement. Rho is required to maintain cell adhesion during movement, but stress fibers and focal adhesions are not required. Finally, Ras regulates focal adhesion and stress fiber turnover and this is essential for cell movement. We conclude that the signal transduction pathways controlled by the four small GTPases, Rho, Rac, Cdc42, and Ras, cooperate to promote cell movement.

0 comments Cited 262 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Autotaxin has lysophospholipase D activity leading to tumor cell growth and motility by lysophosphatidic acid production

Makiko Umezu-Goto, Yasuhiro Kishi, Akitsu Taira … (2002)

Autotaxin (ATX) is a tumor cell motility–stimulating factor, originally isolated from melanoma cell supernatants. ATX had been proposed to mediate its effects through 5′-nucleotide pyrophosphatase and phosphodiesterase activities. However, the ATX substrate mediating the increase in cellular motility remains to be identified. Here, we demonstrated that lysophospholipase D (lysoPLD) purified from fetal bovine serum, which catalyzes the production of the bioactive phospholipid mediator, lysophosphatidic acid (LPA), from lysophosphatidylcholine (LPC), is identical to ATX. The Km value of ATX for LPC was 25-fold lower than that for the synthetic nucleoside substrate, p-nitrophenyl-tri-monophosphate. LPA mediates multiple biological functions including cytoskeletal reorganization, chemotaxis, and cell growth through activation of specific G protein–coupled receptors. Recombinant ATX, particularly in the presence of LPC, dramatically increased chemotaxis and proliferation of multiple different cell lines. Moreover, we demonstrate that several cancer cell lines release significant amounts of LPC, a substrate for ATX, into the culture medium. The demonstration that ATX and lysoPLD are identical suggests that autocrine or paracrine production of LPA contributes to tumor cell motility, survival, and proliferation. It also provides potential novel targets for therapy of pathophysiological states including cancer.

0 comments Cited 208 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Lysophosphatidic acid receptors.

I Ishii, Jerold Chun, James J Contos (2000)

Lysophosphatidic acid (LPA) is a simple bioactive phospholipid with diverse physiological actions on many cell types. LPA induces proliferative and/or morphological effects and has been proposed to be involved in biologically important processes including neurogenesis, myelination, angiogenesis, wound healing, and cancer progression. LPA acts through specific G protein-coupled, seven-transmembrane domain receptors. To date, three mammalian cognate receptor genes, lp(A1)/vzg-1/Edg2, lp(A2)/Edg4, and lp(A3)/Edg7, have been identified that encode high-affinity LPA receptors. Here, we review current knowledge on these LPA receptors, including their isolation, function, expression pattern, gene structure, chromosomal location, and possible physiological or pathological roles.

0 comments Cited 58 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Journal ID (nlm-ta): J Cell Biol

Title: The Journal of Cell Biology

Publisher: The Rockefeller University Press

ISSN (Print): 0021-9525

ISSN (Electronic): 1540-8140

Publication date (Print): 22 July 2002

Volume: 158

Issue: 2

Pages: 197-199

Affiliations

Division of Cellular Biochemistry and Centre for Biomedical Genetics, Netherlands Cancer Institute, 1066 CX Amsterdam, Netherlands

Author notes

Address correspondence to Wouter H. Moolenaar, Division of Cellular Biochemistry, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, Netherlands. Tel.: 31-20-512-1971. Fax: 31-20-512-1989. E-mail: w.moolenaar@ 123456nki.nl

Article

Publisher ID: 200206094

DOI: 10.1083/jcb.200206094

PMC ID: 2173118

PubMed ID: 12135981

SO-VID: 1959593f-f2cd-4208-b954-a8634b54ee9e

History

Date received : 20 June 2002

Date accepted : 27 June 2002

Comments

Comment on this article

scite_

Smart Citations

Citing PublicationsSupportingMentioningContrasting

View Citations

See how this article has been cited at scite.ai

scite shows how a scientific paper has been cited by providing the context of the citation, a classification describing whether it supports, mentions, or contrasts the cited claim, and a label indicating in which section the citation was made.