PLA2 and PI3K/PTEN Pathways Act in Parallel to Mediate Chemotaxis

Lingfeng Chen; Miho Iijima; Ming Tang; Mark A. Landree; Yi Elaine Huang; Yuan Xiong; Pablo A. Iglesias; Peter N. Devreotes

doi:10.1016/j.devcel.2007.03.005

PLA₂ and PI3K/PTEN Pathways Act in Parallel to Mediate Chemotaxis

Lingfeng Chen, Miho Iijima, Ming Tang, Mark A. Landree, Yi Elaine Huang, Yuan Xiong, Pablo A. Iglesias, Peter N. Devreotes

Research output: Contribution to journal › Article › peer-review

157 Scopus citations

Abstract

Directed cell migration involves signaling events that lead to local accumulation of PI(3,4,5)P₃, but additional pathways act in parallel. A genetic screen in Dictyostelium discoideum to identify redundant pathways revealed a gene with homology to patatin-like phospholipase A₂. Loss of this gene did not alter PI(3,4,5)P₃ regulation, but chemotaxis became sensitive to reductions in PI3K activity. Likewise, cells deficient in PI3K activity were more sensitive to inhibition of PLA₂ activity. Deletion of the PLA₂ homolog and two PI3Ks caused a strong defect in chemotaxis and a reduction in receptor-mediated actin polymerization. In wild-type cells, chemoattractants stimulated a rapid burst in an arachidonic acid derivative. This response was absent in cells lacking the PLA₂ homolog, and exogenous arachidonic acid reduced their dependence on PI3K signaling. We propose that PLA₂ and PI3K signaling act in concert to mediate chemotaxis, and metabolites of PLA₂ may be important mediators of the response.

Original language	English (US)
Pages (from-to)	603-614
Number of pages	12
Journal	Developmental Cell
Volume	12
Issue number	4
DOIs	https://doi.org/10.1016/j.devcel.2007.03.005
State	Published - Apr 2007

Keywords

CELLBIO
SIGNALING

ASJC Scopus subject areas

Molecular Biology
Biochemistry, Genetics and Molecular Biology(all)
Developmental Biology
Cell Biology

Access to Document

10.1016/j.devcel.2007.03.005

Cite this

@article{4518032a9ef14d379c1f2bb0cbf0d6aa,

title = "PLA2 and PI3K/PTEN Pathways Act in Parallel to Mediate Chemotaxis",

abstract = "Directed cell migration involves signaling events that lead to local accumulation of PI(3,4,5)P3, but additional pathways act in parallel. A genetic screen in Dictyostelium discoideum to identify redundant pathways revealed a gene with homology to patatin-like phospholipase A2. Loss of this gene did not alter PI(3,4,5)P3 regulation, but chemotaxis became sensitive to reductions in PI3K activity. Likewise, cells deficient in PI3K activity were more sensitive to inhibition of PLA2 activity. Deletion of the PLA2 homolog and two PI3Ks caused a strong defect in chemotaxis and a reduction in receptor-mediated actin polymerization. In wild-type cells, chemoattractants stimulated a rapid burst in an arachidonic acid derivative. This response was absent in cells lacking the PLA2 homolog, and exogenous arachidonic acid reduced their dependence on PI3K signaling. We propose that PLA2 and PI3K signaling act in concert to mediate chemotaxis, and metabolites of PLA2 may be important mediators of the response.",

keywords = "CELLBIO, SIGNALING",

author = "Lingfeng Chen and Miho Iijima and Ming Tang and Landree, {Mark A.} and Huang, {Yi Elaine} and Yuan Xiong and Iglesias, {Pablo A.} and Devreotes, {Peter N.}",

note = "Funding Information: Research was supported by Public Health Services grants 28007 and 34933 to P.N.D., by Leukemia and Lymphoma Society Fellowship 3374-05 to M.I., and by American Cancer Society Fellowship PF-02-109-01-DDC to M.A.L. Sequence data for D. discoideum were obtained from the dictyBase website at http://www.dictybase.org/ . We thank Dr. Daniel M. Raben for his technical support and suggestions for lipid analyses. We thank Dr. Richard A. Firtel for the pi3k1 − /2 − cell line. ",

year = "2007",

month = apr,

doi = "10.1016/j.devcel.2007.03.005",

language = "English (US)",

volume = "12",

pages = "603--614",

journal = "Developmental Cell",

issn = "1534-5807",

publisher = "Cell Press",

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T1 - PLA2 and PI3K/PTEN Pathways Act in Parallel to Mediate Chemotaxis

AU - Chen, Lingfeng

AU - Iijima, Miho

AU - Tang, Ming

AU - Landree, Mark A.

AU - Huang, Yi Elaine

AU - Xiong, Yuan

AU - Iglesias, Pablo A.

AU - Devreotes, Peter N.

N1 - Funding Information: Research was supported by Public Health Services grants 28007 and 34933 to P.N.D., by Leukemia and Lymphoma Society Fellowship 3374-05 to M.I., and by American Cancer Society Fellowship PF-02-109-01-DDC to M.A.L. Sequence data for D. discoideum were obtained from the dictyBase website at http://www.dictybase.org/ . We thank Dr. Daniel M. Raben for his technical support and suggestions for lipid analyses. We thank Dr. Richard A. Firtel for the pi3k1 − /2 − cell line.

PY - 2007/4

Y1 - 2007/4

N2 - Directed cell migration involves signaling events that lead to local accumulation of PI(3,4,5)P3, but additional pathways act in parallel. A genetic screen in Dictyostelium discoideum to identify redundant pathways revealed a gene with homology to patatin-like phospholipase A2. Loss of this gene did not alter PI(3,4,5)P3 regulation, but chemotaxis became sensitive to reductions in PI3K activity. Likewise, cells deficient in PI3K activity were more sensitive to inhibition of PLA2 activity. Deletion of the PLA2 homolog and two PI3Ks caused a strong defect in chemotaxis and a reduction in receptor-mediated actin polymerization. In wild-type cells, chemoattractants stimulated a rapid burst in an arachidonic acid derivative. This response was absent in cells lacking the PLA2 homolog, and exogenous arachidonic acid reduced their dependence on PI3K signaling. We propose that PLA2 and PI3K signaling act in concert to mediate chemotaxis, and metabolites of PLA2 may be important mediators of the response.

AB - Directed cell migration involves signaling events that lead to local accumulation of PI(3,4,5)P3, but additional pathways act in parallel. A genetic screen in Dictyostelium discoideum to identify redundant pathways revealed a gene with homology to patatin-like phospholipase A2. Loss of this gene did not alter PI(3,4,5)P3 regulation, but chemotaxis became sensitive to reductions in PI3K activity. Likewise, cells deficient in PI3K activity were more sensitive to inhibition of PLA2 activity. Deletion of the PLA2 homolog and two PI3Ks caused a strong defect in chemotaxis and a reduction in receptor-mediated actin polymerization. In wild-type cells, chemoattractants stimulated a rapid burst in an arachidonic acid derivative. This response was absent in cells lacking the PLA2 homolog, and exogenous arachidonic acid reduced their dependence on PI3K signaling. We propose that PLA2 and PI3K signaling act in concert to mediate chemotaxis, and metabolites of PLA2 may be important mediators of the response.

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