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PMID: 12802064 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Receptor-mediated regulation of PI3Ks confines PI(3,4,5)P3 to the leading edge of chemotaxing cells.

Molecular biology of the cell ·Vol. 14 ·No. 5 ·2003-05-00 ·Pages 1913-22

Huang YE, Iijima M, Parent CA, Funamoto S, Firtel RA, Devreotes P

Abstract

Recent studies have demonstrated that PH domains specific for PI(3,4,5)P3 accumulate at the leading edge of a number of migrating cells and that PI3Ks and PTEN associate with the membrane at the front and back, respectively, of chemotaxing Dictyostelium discoideum cells. However, the dependence of chemoattractant induced changes in PI(3,4,5)P3 on PI3K and PTEN activities have not been defined. We find that bulk PI(3,4,5)P3 levels increase transiently upon chemoattractant stimulation, and the changes are greater and more prolonged in pten- cells. PI3K activation increases within 5 s of chemoattractant addition and then declines to a low level of activity identically in wild-type and pten- cells. Reconstitution of the PI3K activation profile can be achieved by mixing membranes from stimulated pi3k1-/pi3k2- cells with cytosolic PI3Ks from unstimulated cells. These studies show that significant control of chemotaxis occurs upstream of the PI3Ks and that regulation of the PI3Ks and PTEN cooperate to shape the temporal and spatial localization of PI(3,4,5)P3.

MeSH Terms
Animals Cell Membrane/metabolism Chemotaxis/physiology Dictyostelium/enzymology Guanosine 5'-O-(3-Thiotriphosphate)/metabolism PTEN Phosphohydrolase Phosphatidylinositol 3-Kinases/metabolism Phosphatidylinositols/metabolism Phosphoric Monoester Hydrolases/metabolism Protein Kinases/metabolism Tumor Suppressor Proteins/metabolism
Chemicals
Phosphatidylinositols Tumor Suppressor Proteins phosphoinositide-3,4,5-triphosphate Guanosine 5'-O-(3-Thiotriphosphate) Protein Kinases Phosphatidylinositol 3-Kinases YakA protein, Dictyostelium discoideum Phosphoric Monoester Hydrolases PTEN Phosphohydrolase
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Huang Yi Elaine
Department of Cell Biology, Johns Hopkins University, School of Medicine, Baltimore, Maryland 21205, USA.
Iijima Miho
Parent Carole A
Funamoto Satoru
Firtel Richard A
Devreotes Peter
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Article Info
Journal
Molecular biology of the cell
Abbr.
Mol Biol Cell
ISSN
1059-1524
DOI
10.1091/mbc.e02-10-0703
Published
2003-05-00
Epub
2003-00-06
Pages
1913-22
Language
English
Region
United States
NLM ID
9201390
PMCID
PMC165086
Subset
IM
Grants
NIGMS NIH HHS · R01 GM034933 · United States
PHS HHS · 29007 · United States
NIGMS NIH HHS · GM34933 · United States
External Links
PubMed source DOI: 10.1091/mbc.e02-10-0703 PMC Full Text View journal details
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