Spatial and temporal regulation of 3-phosphoinositides by PI 3-kinase and PTEN mediates chemotaxis

被引：607

作者：

Funamoto, S ^{[1
]}

Meili, R ^{[1
]}

Lee, S ^{[1
]}

Parry, L ^{[1
]}

Firtel, RA ^{[1
]}

机构：

[1] Univ Calif San Diego, Ctr Mol Genet, Div Biol, Sect Cell & Dev Biol, La Jolla, CA 92093 USA

来源：

CELL | 2002年 / 109卷 / 05期

关键词：

D O I：

10.1016/S0092-8674(02)00755-9

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

We have investigated the mechanisms of leading edge formation in chemotaxing Dictyostelium cells. We demonstrate that while phosphatidylinositol 3-kinase (PI3K) transiently translocates to the plasma membrane in response to chemoattractant stimulation and to the leading edge in chemotaxing cells, PTEN, a negative regulator of PI3K pathways, exhibits a reciprocal pattern of localization. By uniformly localizing PI3K along the plasma membrane, we show that chemotaxis pathways are activated along the lateral sides of cells and PI3K can initiate pseudopod formation, providing evidence for a direct instructional role of PI3K in leading edge formation. These findings provide evidence that differential subcellular localization and activation of PI3K and PTEN is required for proper chemotaxis.

引用

页码：611 / 623

页数：13

共 37 条

[1] Efficient control of gene expression by a tetracycline-dependent transactivator in single Dictyostelium discoideum cells [J].

Blaauw, M ;

Linskens, MHK ;

van Haastert, PJM .

GENE, 2000, 252 (1-2) :71-82

[2] Signaling pathways controlling cell polarity and chemotaxis [J].

Chung, CY ;

Funamoto, S ;

Firtel, RA .

TRENDS IN BIOCHEMICAL SCIENCES, 2001, 26 (09) :557-566

[3] PAKa, a putative PAK family member, is required for cytokinesis and the regulation of the cytoskeleton in Dictyostelium discoideum cells during chemotaxis [J].

Chung, CY ;

Firtel, RA .

JOURNAL OF CELL BIOLOGY, 1999, 147 (03) :559-575

[4] Control of cell polarity and chemotaxis by Akt/PKB and PI3 kinase through the regulation of PAKa [J].

Chung, CY ;

Potikyan, G ;

Firtel, RA .

MOLECULAR CELL, 2001, 7 (05) :937-947

[5] Identification of pleckstrin-homology-domain-containing proteins with novel phosphoinositide-binding specificities [J].

Dowler, S ;

Currie, RA ;

Campbell, DG ;

Deak, M ;

Kular, G ;

Downes, CP ;

Alessi, DR .

BIOCHEMICAL JOURNAL, 2000, 351 (01) :19-31

[6]

Firtel RA, 2000, BIOESSAYS, V22, P603, DOI 10.1002/1521-1878(200007)22:7<603::AID-BIES3>3.0.CO

[7]

2-#

[8] Mutation of the pleckstrin homology domain of Bruton's tyrosine kinase in immunodeficiency impaired inositol 1,3,4,5-tetrakisphosphate binding capacity [J].

Fukuda, M ;

Kojima, T ;

Kabayama, H ;

Mikoshiba, K .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (48) :30303-30306

[9] Haematopoietic cell-specific CDM family protein DOCK2 is essential for lymphocyte migration [J].

Fukui, Y ;

Hashimoto, O ;

Sanui, T ;

Oono, T ;

Koga, H ;

Abe, M ;

Inayoshi, A ;

Noda, M ;

Oike, M ;

Shirai, T ;

Sasazuki, T .

NATURE, 2001, 412 (6849) :826-831

[10] Role of phosphatidylinositol 3′ kinase and a downstream pleckstrin homology domain-containing protein in controlling chemotaxis in Dictyostelium [J].

Funamoto, S ;

Milan, K ;

Meili, R ;

Firtel, RA .

JOURNAL OF CELL BIOLOGY, 2001, 153 (04) :795-809

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