Non-invasive visualization of the lipid product of class I PI3K in transgenic mouse models. (20th March 2007)

• Record Type: Journal Article
• Authors: Sasaki, T.; Sasaki, J.; Watanabe, K.; Suzuki, A.
• Is Part Of: Biochemical Society transactions. Volume 35:Number 2(2007)
• Page Start: 215
• Page End: 218
• Publication Date: 2007-03-20
• Subjects: lipid product -- neutrophil -- phosphatidylinositol 3, 4, 5-trisphosphate -- phosphoinositide 3-kinase (PI3K) -- Src homology 2-containing inositol phosphatase-1 (SHIP1) -- transgenic mouse model; Biochemistry -- Congresses; 572
• DOI: 10.1042/BST0350215
• Languages: English
• ISSNs: 0300-5127

Abstract

Abstract : PI3Ks (phosphoinositide 3-kinases) regulate many critical cellular responses by producing PI(3, 4, 5) P 3 (phosphatidylinositol 3, 4, 5-trisphosphate). To facilitate the spatio-temporal characterization of PI(3, 4, 5) P 3 in living primary cells, we generated a novel strain of transgenic mice [ AktPH (Akt pleckstrin homology domain)– GFP (green fluorescent protein) Tg (transgenic) mice] that express a fluorescent bioprobe for PI(3, 4, 5) P 3 /PI(3, 4) P 2 (phosphatidylinositol 3, 4-bisphosphate). By crossing AktPH–GFP Tg mice with strains of gene-targeted 'knockout' mice lacking a particular phosphoinositide-metabolizing enzyme, we have been able to evaluate the contribution of each enzyme to PI(3, 4, 5) P 3 localization in migrating neutrophils. Our results indicate that PI3Kγ and the PI(3, 4, 5) P 3 phosphatase SHIP1 [SH2 (Src homology 2)-containing inositol phosphatase-1] are the key regulators of PI(3, 4, 5) P 3 dynamics during fMet-Leu-Phe ( N -formylmethionyl-leucylphenylalanine; 'chemotactic peptide')-stimulated neutrophil migration. Our study has also validated the fluorescent transgenic strategy for studying PI(3, 4, 5) P 3 metabolism in physiological and pathological situations.