A membrane‐permeant ester of phosphatidylinositol 3,4,5‐trisphosphate (PIP3) is an activator of human neutrophil migration

FEBS Letters

Niggli, Verena¹ 

[1] Department of Pathology, University of Bern, Murtenstr. 31, P.O. Box 62, CH-3010 Bern, Switzerland

关键词: Neutrophil;    Cell migration;    Phosphatidylinositol 3;    4;    5-trisphosphate;    Rho-activated kinase;    Phosphatidylinositol 3-kinase;    fNLPNTL;    N-formyl-L-norleucyl-L-leucyl-L-phenylalanyl-L-norleucyl-L-tyrosyl-L-lysine;    ERK;    extracellular signal-regulated kinase;    HSA;    human serum albumin;    MAPK;    mitogen-activated protein kinase;    PI 3-kinase;    phosphatidylinositol 3-kinase;    PI(3;    4)P2;    phosphatidylinositol 3;    4-diphosphate;    PIP3;    phosphatidylinositol 3;    4;    5-trisphosphate;    PIP3/AM;    dilauroyl phosphatidylinositol 3;    4;    5-trisphosphate-heptakis-(acetooxymethyl)ester;   

DOI  :  10.1016/S0014-5793(00)01534-9

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Activity of phosphatidylinositol (PI) 3-kinase is required for optimal migration of human neutrophils [Niggli and Keller (1999) Eur. J. Pharmacol. 335, 43–52]. We have tested the direct effect of a product of PI 3-kinase, phosphatidylinositol 3,4,5-trisphosphate (PIP₃), on neutrophil migration. To this end, a membrane-permeant ester of PIP₃, dilauroyl phosphatidylinositol 3,4,5-trisphosphate-heptakis-(acetooxymethyl)ester (PIP₃/AM) was used. PIP₃/AM (ED₅₀: 10–17 μM) induced development of polarity and accumulation of F-actin in the leading lamellae in up to 70% of the cells. These cells exhibited stimulated random migration, comparable to that observed in uniform concentrations of chemotactic peptide. Evidence is provided for a role of Rho-kinase and for activation of PI 3-kinase in a positive feedback loop in PIP₃/AM-induced motility.

【 授权许可】

Unknown