論文 - 詳細
RRC ID | 29040 |
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著者 | Iijima M, Devreotes P. |
タイトル | Tumor suppressor PTEN mediates sensing of chemoattractant gradients. |
ジャーナル | Cell |
Abstract |
Shallow gradients of chemoattractants, sensed by G protein-linked signaling pathways, elicit localized binding of PH domains specific for PI(3,4,5)P3 at sites on the membrane where rearrangements of the cytoskeleton and pseudopod extension occur. Disruption of the PI 3-phosphatase, PTEN, in Dictyostelium discoideum dramatically prolonged and broadened the PH domain relocation and actin polymerization responses, causing the cells lacking PTEN to follow a circuitous route toward the attractant. Exogenously expressed PTEN-GFP localized to the surface membrane at the rear of the cell. Membrane localization required a putative PI(4,5)P2 binding motif and was required for chemotaxis. These results suggest that specific phosphoinositides direct actin polymerization to the cell's leading edge and regulation of PTEN through a feedback loop plays a critical role in gradient sensing and directional migration. |
巻・号 | 109(5) |
ページ | 599-610 |
公開日 | 2002-5-31 |
DOI | 10.1016/s0092-8674(02)00745-6 |
PII | S0092867402007456 |
PMID | 12062103 |
MeSH | Actin Cytoskeleton / metabolism* Animals Cell Membrane / metabolism* Cell Polarity / physiology Chemotaxis / physiology* Cytosol / metabolism Dictyostelium / cytology Dictyostelium / enzymology* Dictyostelium / genetics Down-Regulation / physiology Green Fluorescent Proteins Indicators and Reagents / metabolism Luminescent Proteins / metabolism Mutation / genetics Nucleotides, Cyclic / genetics Nucleotides, Cyclic / metabolism PTEN Phosphohydrolase Phosphatidylinositol Phosphates / metabolism* Phosphatidylinositols / metabolism Phosphoric Monoester Hydrolases / deficiency* Phosphoric Monoester Hydrolases / genetics Polymers / metabolism Protein Structure, Tertiary / physiology Pseudopodia / metabolism* Pseudopodia / ultrastructure Tumor Suppressor Proteins / deficiency* Tumor Suppressor Proteins / genetics |
IF | 38.637 |
引用数 | 498 |
WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY |
リソース情報 | |
細胞性粘菌 | S00005 |