期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2009
卷号：106
期号：48
页码：20312-20317
DOI：10.1073/pnas.0905506106
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Class IB phosphoinositide 3-kinase {gamma} (PI3K{gamma}) elicits various immunologic and cardiovascular responses; however, the molecular basis for this signal heterogeneity is unclear. PI3K{gamma} consists of a catalytic p110{gamma} and a regulatory p87PIKAP (p87, also p84) or p101 subunit. Hitherto p87 and p101 are generally assumed to exhibit redundant functions in receptor-induced and G protein {beta}{gamma} (G{beta}{gamma})-mediated PI3K{gamma} regulation. Here we investigated the molecular mechanism for receptor-dependent p87/p110{gamma} activation. By analyzing GFP-tagged proteins expressed in HEK293 cells, PI3K{gamma}-complemented bone marrow-derived mast cells (BMMCs) from p110{gamma}-/- mice, and purified recombinant proteins reconstituted to lipid vesicles, we elucidated a novel pathway of p87-dependent, G protein-coupled receptor (GPCR)-induced PI3K{gamma} activation. Although p101 strongly interacted with G{beta}{gamma
关键词：confocal life cell imaging ; G protein ; receptor signaling ; mast cells
