Publication Information

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[89], 'response.1–3': [90], 'Class': [91, 177, 199, 314, 336], 'PI3Ks': [93, 179, 201, 338, 974], 'are': [94, 127, 202, 339, 486, 507, 856, 942, 1194, 1339, 1449, 1493, 1734, 1786, 1833], 'enzymes': [95, 708], 'that': [96, 265, 301, 448, 472, 539, 597, 603, 623, 715, 827, 878, 886, 902, 982, 992, 1171, 1195, 1297, 1310, 1454, 1467, 1553, 1658, 1678, 1714, 1754], 'selectively': [97, 813, 2420], 'phosphorylate': [98], '3′-OH': [100], 'position': [101], 'PtdIns(4,5)P2': [104], 'inositol': [105, 119, 1957], 'ring': [106], 'vivo': [108, 613], 'generate': [110], 'PtdIns(3,4,5)P3,': [111], 'which': [112, 217, 575, 1008], 'then': [113, 604], 'can': [114, 803], 'be': [115, 784, 804, 812, 891], 'further': [116, 183], 'metabolized': [117], 'by': [118, 192, 261, 342, 469, 477, 489, 607, 644, 1055, 1212, 1240, 1244, 1291, 1418, 1483, 1566, 1644, 1711, 1849, 2318, 2476, 2534, 2973], 'lipid': [120, 571, 734, 767, 789, 1604, 1631, 1922, 2090, 2570], 'phosphatases': [121], 'PtdIns(3,4)P2.': [123], 'PtdIns(3,4)P2': [124, 625], 'PtdIns(3,4,5)P3': [126, 627, 658, 1499], 'nominally': [128], 'absent': [129], 'resting': [131], 'cells,': [132], 'rise': [133], 'briskly': [134], 'response': [136, 2862], 'PI3K': [140, 249, 316, 427, 451, 458, 565, 707, 788, 872, 954, 1113, 1176, 1200, 1230, 1484, 1545, 1683, 1716, 1762], 'activation': [141, 191, 378, 388, 445, 465, 528, 648, 1051, 1180, 1211, 1239, 1290, 1352, 1431, 1482, 1505, 1521, 1534, 2031, 2392], 'during': [142, 1082, 1145, 1803], 'cellular': [143, 175, 717, 1744], 'stimulation,': [144], 'function': [146, 732, 1954], 'membrane': [151, 271, 581, 685, 1037, 1594], 'trafficking': [152], 'largely': [153], 'as': [154, 733, 779, 900, 1489, 1549, 1613, 1637, 1784, 1792], 'a': [155, 172, 206, 226, 256, 295, 332, 416, 516, 536, 594, 620, 661, 807, 905, 917, 1010, 1025, 1077, 1123, 1156, 1167, 1283, 1511, 1638, 1782, 2005, 2128, 2602, 2696, 2702], 'result': [156], 'their': [158, 186, 234, 462, 731], 'interaction': [159, 247, 519, 584], 'with': [160, 274, 331, 504, 520, 628, 693, 797, 806, 823, 944, 996, 1268, 1451, 1661, 1718], 'pleckstrin': [161], 'homology': [162], '(PH)': [163], 'domains': [164, 264, 300, 699, 2592], '(≈100': [165], 'amino': [166], 'acid': [167], '3-phosphoinositide': [168], 'binding': [169, 328], 'modules)': [170], 'range': [173], 'proteins.': [176, 288], 'subclassified': [182], 'according': [184, 460], 'structure': [187, 423, 1694], 'mode': [189], 'cell': [193, 721, 909, 921, 947, 959, 1269, 1925], 'surface': [194], 'receptors': [195, 434, 1331, 1338, 1980, 2066, 2422], '(Figure,': [196, 1233], 'panel': [197, 1234], 'A).': [198], 'IA': [200, 514, 1654, 2596], 'heterodimers': [203], 'composed': [204, 318], 'catalytic': [207, 238, 322, 354, 484, 1461, 1656, 2186], 'subunit': [208, 229, 323, 327, 355, 369, 502, 524, 762, 1690, 1725, 2133, 2187, 2600], '(the': [209], 'ubiquitous': [210], 'p110α,': [211], 'more': [212, 1561], 'tissue-restricted': [213], 'p110β,': [214], 'or': [215, 233, 285, 1107, 1328, 1435, 1514, 1840], 'p110δ': [216], 'is': [218, 251, 317, 415, 474, 535, 573, 576, 834, 883, 964, 1129, 1140, 1242, 1248, 1266, 1308, 1404, 1428, 1539, 1569, 1584, 1598, 1709, 1781, 2004, 2538, 2693], 'confined': [219], 'hematopoietic': [221], 'cells)': [222], 'tightly': [223], 'complexed': [224], 'regulatory': [227, 291, 334, 368, 523, 704, 761, 1689, 1724, 1821, 2599], 'adapter': [228, 1666], '(p85α,': [230], 'p85β,': [231], 'p55,': [232], 'splice': [235], 'variants).': [236], 'All': [237], 'subunits': [239, 254, 292, 485, 1462, 1657, 2028], 'bind': [240], 'Ras,': [241], 'but': [242, 383, 915, 1209, 1262, 1319, 1346, 1374, 2606], 'role': [244, 907, 971, 1012, 1060, 1174, 1918, 2056, 2216, 2248, 2603, 2760], 'this': [246, 751, 824, 1150, 1567, 1767, 1812, 1831], 'signaling': [250, 563, 1139, 1380, 1413, 1617, 1759, 1984, 2062], 'uncertain.': [252], 'Regulatory': [253], 'harbor': [255], 'C-terminal': [257], 'p110-binding': [258], 'region': [259], 'flanked': [260], 'two': [262], 'SH2': [263, 698], 'dock': [266], 'holoenzyme': [268, 310, 1708], 'through': [272, 446, 582, 1576, 1674, 1986, 2391, 2932], 'interactions': [273, 305, 503], 'specific': [275, 637, 2247], 'phosphotyrosyl-containing': [276], 'sequences': [277], 'within': [278], 'C-terminus': [280], 'receptor': [282, 349, 480, 776, 994, 1015, 1179, 1214, 1379, 2320, 2644], 'tyrosine': [283, 481, 495, 545, 1215, 1343, 1382, 1680], 'kinases': [284, 1645, 1681, 2100], 'other': [286, 303, 512], 'membrane-associated': [287], 'Larger': [289], 'p85': [290, 326, 498, 501, 522, 703, 760, 1731], 'also': [293, 525, 1067, 1486], 'contain': [294], 'series': [296, 1168], 'N-terminal': [298, 1691, 1732, 2591], 'modular': [299, 1692], 'specify': [302], 'protein-protein': [304], 'dictate': [307], 'differences': [308, 1375, 1409], 'targeting': [311, 686, 2564], 'regulation.': [313], 'IB': [315, 337], 'p110γ': [321, 353, 377, 403, 911], '(lacking': [324], 'region)': [329], 'associated': [330, 759], 'p101': [333, 366, 375, 395], 'protein.': [335], 'specifically': [340, 1574], 'stimulated': [341], 'Gβγ': [343, 2501], 'dimers': [344, 1300, 2502], 'liberated': [345], 'upon': [346], 'G': [347, 1978, 2064, 2218, 2853, 2920, 2933, 3020], 'protein–coupled': [348], '(GPCR)': [350], 'activation.': [351, 615, 1335, 2011], 'The': [352, 876, 1059, 1110, 1191, 1397, 1477, 1648, 1685, 1764, 1917, 2276, 2304, 3025], 'contains': [356, 619], 'all': [357, 1199], 'structural': [359], 'elements': [360], 'necessary': [361], 'for': [362, 569, 641, 770, 845, 858, 952, 1112, 1286, 1479, 1616, 1622, 1672, 1737, 1761, 1800, 2057, 2127, 2217, 2540], 'Gβγ-induced': [363, 2030], 'stimulation;': [364], 'noncatalytic': [367], 'differentially': [370], 'modulates': [371], 'its': [372, 586, 673, 758], 'kinase': [373, 393, 654, 743, 768, 792, 820, 830, 1126, 1216, 1344, 1383, 1547, 2010, 2093, 2307], 'activity.': [374, 744, 821], 'supports': [376, 1313], 'c-Jun': [380], 'amino-terminal': [381], 'kinase,': [382], 'has': [384, 466, 848, 1068, 1115, 1527, 1634], 'little': [385], 'effect': [386], 'on': [387, 969, 1166, 2705], 'signal–regulated': [391], 'protein': [392, 653, 791, 829, 846, 1546, 1698, 2092, 2099], '(ERK).4,5': [394], 'alters': [396], 'substrate': [398, 753], 'preference': [399], 'Gβγ-stimulated': [401], 'p110γ;': [402], 'alone': [404], 'preferentially': [405], 'phosphorylates': [406, 756], 'PtdIns': [407], 'form': [409, 1659, 1721], 'PtdIns(3)P,': [410], 'whereas': [411, 1093], 'p101/p110γ': [413], 'heterodimer': [414], 'highly': [417], 'PtdIns(4,5)P2-selective': [418], 'enzyme.6Download': [419], 'figureDownload': [420], 'PowerPointA,': [421], 'Domain': [422], '1': [426, 1897], 'isoforms.': [428, 657, 1579], 'B,': [429, 1935, 2414, 2441, 2445, 2472, 2498], 'PDGF': [430, 1241, 1327, 1400, 1430], 'angiotensin': [432, 1226, 1295, 1329, 1350, 1377, 2454, 2857], 'II': [433, 1296, 1330, 1337, 1351, 1378], 'rat': [436, 984, 1187, 2685, 2774, 3004], 'protal': [437], 'vein': [438, 1189], 'myocytes': [439, 1251], 'couple': [440, 2421], 'L-type': [442, 1183, 1205, 1236, 1287, 1531, 1772, 1793, 2425, 2458, 2505, 2970], 'calcium': [443, 1020, 1184, 1206, 1237, 1288, 1316, 1333, 1442, 1480, 1532, 1556, 1623, 1773, 1794, 1801, 2459], 'channel': [444, 1207, 1210, 1238, 1289, 1317, 1334, 1481, 1502, 1533, 1557, 1774], 'involve': [449], 'distinct': [450, 940, 950, 1229, 1577, 1652, 1665, 2477], 'isoforms.The': [452, 566], 'convenient': [453], 'classification': [454], 'isoforms': [459, 955, 1177, 1201, 1485, 2037, 2419], 'mechanism': [463, 1111, 1478, 1552, 1583, 1597, 1639, 1671], 'challenged': [468], 'evidence': [471, 901, 1453, 1713], 'PI3Kβ': [473, 553], 'synergistically': [475], 'activated': [476, 488, 2351], 'GPCRs': [478], 'kinases.': [482, 1905], 'p110β': [483, 1276, 1460, 1470], 'directly': [487], 'membrane-bound': [490], 'βγ': [491], 'dimers;': [492], 'Gα': [493], 'subunits,': [494, 499], 'phosphorylation': [496, 643, 847], 'phosphotyrosine-containing': [505, 694], 'proteins': [506, 695, 1667], 'not': [508, 818, 849, 1263, 1405, 1423, 1620, 1735, 1834, 2607], 'required.7': [509], 'However,': [510, 799, 1790], 'like': [511], 'enzymes,': [515], 'phosphotyrosyl': [517, 1314], 'peptide': [518], 'leads': [526, 1086, 1202], 'PI3Kβ.': [530, 1245], 'Hence,': [531, 706], 'p85/p110β': [533], 'complex': [534], 'coincidence': [537], 'detector': [538], 'integrates': [540], 'signals': [541, 714, 802, 2094], 'from': [542, 720, 1254, 1302, 2063, 2387, 2856], 'GPCR-': [543], 'kinase–signaling': [546], 'cascades.': [547], 'Differential': [548, 2563, 2759], 'expression': [549, 1197, 1322, 1471], 'regulation': [551, 1016, 1643, 1703, 1775, 2927], 'PI3Kγ': [555, 738, 808, 833, 1004, 1028, 1391, 2096, 2795, 3029, 3082], 'extends': [556], 'repertoire': [558, 1757], 'specificity': [560, 1673, 1760], 'GPCR': [562, 1219, 1293], 'best-characterized': [567], 'target': [568, 844], 'PI3K-derived': [570], 'products': [572, 1923], 'Akt,': [574, 617], 'recruited': [577], 'plasma': [580], 'between': [585, 1385], 'PH': [587, 621, 662, 683], 'domain': [588, 622, 663, 1693], '3′-phosphorylated': [590, 800, 854], 'phosphoinositides.2': [591], 'This': [592, 1022, 1246, 1278, 1596], 'promotes': [593], 'conformational': [595], 'change': [596], 'exposes': [598], 'Thr-308': [599], 'Ser-473': [601], 'residues': [602], 'become': [605], 'phosphorylated': [606], 'PDK1,': [608], 'resulting': [609], 'full': [611], 'enzyme': [614], 'Like': [616], 'PDK1': [618, 632, 645, 1507], 'binds': [624, 659], 'high': [629], 'affinity,': [630], 'ensuring': [631], 'Akt': [634, 1523, 1526, 2355], 'colocalization': [635], 'at': [636, 696], 'membranes.': [638], 'Other': [639], 'targets': [640], 'PtdIns(3,4,5)P3-dependent': [642, 1504], 'include': [646], 'loops': [649], 'p70S6-kinase': [651], 'C': [655, 2629, 2728, 2793], '(PKC)': [656], 'nucleotide': [666], 'exchange': [667, 674], 'factor': [668, 1223, 1360, 2316], 'Vav': [669], 'allosterically': [671], 'enhances': [672], 'activity': [675, 769, 793, 831, 1548], 'toward': [676], 'Rac,': [677], 'Cdc42,': [678], 'RhoA,': [680], 'causes': [681], 'domain-mediated': [684], 'phospholipase': [688, 1046, 1053], 'Cγ,': [689, 1047], 'arguably': [691], 'competes': [692], 'Src': [701, 1032, 1354], 'subunits.': [705], 'initiate': [709], 'intricate': [711], 'network': [712], 'influence': [716], 'functions': [718], 'ranging': [719], 'survival,': [722], 'proliferation,': [723], 'migration': [725], 'vesicular': [727], 'trafficking.In': [728], 'addition': [729], 'kinases,': [735], 'PI3Kα': [736, 1062, 1372, 1403, 1434, 1438], 'both': [739], 'intrinsic': [741], 'serine/threonine': [742], 'While': [745], 'most': [746], 'studies': [747, 945, 1170, 1281, 1348, 1770], 'fail': [748], 'consider': [750], 'dual': [752], 'specificity,': [754], 'p100α': [755, 1095], 'itself,': [757], '(which': [763, 1257], 'results': [764, 998, 1448], 'decreased': [766], 'complex),': [772], 'insulin': [775], 'substrate-1.1Inhibitors': [777], 'such': [778], 'wortmannin': [780], 'LY294002': [782], 'cannot': [783, 890], 'used': [785, 869], 'discriminate': [787], 'because': [794, 1525], 'they': [795], 'interfere': [796], 'both.': [798], 'lipid-dependent': [801], 'identified': [805], 'mutant': [809, 825], 'engineered': [810], 'defective': [814, 1249], 'lipid-': [816], '(and': [817, 1090, 1155, 1700], 'protein-)': [819], 'Studies': [822], 'indicate': [826], 'sufficient': [835], 'activate': [837, 1133, 1402], 'ERK': [839], 'cascade': [840], '(although': [841], 'direct': [843, 1496], 'defined).': [851], 'In': [852, 1366, 1444], 'contrast,': [853], 'lipids': [855], 'required': [857, 1736, 2539], 'PI3K/Akt': [859, 2762], 'activation.8Classical': [860], 'gene': [861, 2348], 'knockout': [862], 'strategies': [863], 'mouse': [866, 1073, 1083, 2930], 'examine': [871, 1172], 'isoform': [873], 'selective': [874, 1001], 'functions.': [875, 977], 'observations': [877], 'targeted': [879], 'deletion': [880, 2129], 'p110α': [882, 887, 903, 1259, 1312, 1321, 1458, 2132], 'embryonic-lethal': [884], 'null': [888, 912], 'fibroblasts': [889], 'induced': [892, 2317], 'proliferate': [894], 'culture': [896, 948, 1270], 'taken': [899], 'plays': [904, 1009], 'fundamental': [906, 1817], 'proliferation.9': [910], 'mice': [913, 2125, 2183, 2864], 'survive,': [914], 'display': [916], 'defect': [918, 2120], 'inflammatory': [920], 'migration,': [922, 960], 'abnormal': [923], 'T-cell': [924], 'function,': [925], '(according': [927], 'one': [929, 2694], 'group': [930], 'investigators)': [932], 'increased': [934, 1088, 1204], 'incidence': [935], 'colon': [937], 'tumors.10,11': [938], 'These': [939], 'phenotypes': [941], 'consistent': [943, 1450], 'identifying': [949], 'roles': [951], 'individual': [953, 973], 'mitotic': [957], 'signaling,': [958], 'cytoskeletal': [962, 2605], 'regulation.3There': [963], 'still': [965], 'relatively': [966], 'limited': [967], 'information': [968, 1768], 'cardiovascular': [976], 'A': [978, 2054, 2246, 2634], 'study': [980, 1148, 1158, 1568], 'reported': [981, 1130, 1141, 1621], 'neonatal': [983, 1119], 'cardiomyocytes': [985, 2360, 2386], 'coexpress': [986], 'PI3Kα,': [987], 'β,': [988], 'γ,': [990], 'purinergic': [993, 1014], 'stimulation': [995, 1002, 1439, 2321, 2456], 'ATP': [997, 2672], '(rather': [1005], 'than': [1006], 'PI3Kβ),': [1007], 'critical': [1011], 'spontaneous': [1018], 'IP3-induced': [1019], 'spiking.': [1021], 'occurs': [1023], 'via': [1024, 2508, 2687], 'pathway': [1026, 1128, 1247, 1285, 1517, 1799, 1985, 2280, 2310, 2763], 'involving': [1027], 'Fyn': [1030], '(a': [1031, 1041, 1740], 'family': [1033, 1043], 'kinase)': [1034], 'activation,': [1035, 1318, 1373], 'PIP3-induced': [1036], 'anchoring': [1038], 'Tec': [1040, 1056], 'Btk': [1042], 'member)': [1044], 'concerted': [1050], 'Cγ': [1054], 'Fyn.12': [1058], 'normal': [1064], 'developmental': [1065], 'growth': [1066, 1222, 1359, 2536], 'examined': [1070], 'heart.': [1074], 'Expression': [1075], 'constitutively': [1078], 'active': [1079], 'p85-p100α': [1080], 'chimera': [1081], 'heart': [1084, 1089, 1778, 2282, 2686, 2931], 'development': [1085], 'cardiomyocyte)': [1091], 'size,': [1092], 'dominant-negative': [1094], 'induces': [1096, 1102], 'reciprocal': [1098], 'phenotype.13': [1099], 'Neither': [1100], 'construct': [1101], 'abnormalities': [1103], 'cardiac': [1105, 1807, 1820, 2323], 'architecture/morphology': [1106], 'chamber': [1108], 'function.': [1109, 1926], 'action': [1114], 'explored': [1117], 'cardiomyocyte': [1120], 'cultures,': [1121], 'where': [1122], 'PI3K-Akt-glycogen': [1124], 'synthase': [1125, 2306], '3β': [1127], 'transcriptionally': [1132], 'atrial': [1134, 2314], 'natriuretic': [1135, 2315], 'factor14': [1136], 'PI3K-Akt': [1138], 'induce': [1143], 'cardioprotection': [1144], 'ischemic': [1146], 'insults.15,16A': [1147], 'issue': [1151, 2704], 'Circulation': [1153, 2976], 'Research': [1154], 'companion': [1157], 'Journal': [1161, 2712, 2736, 2867, 3037], 'Biological': [1163, 3079], 'Chemistry)': [1164], 'follows': [1165, 1228], 'voltage-gated': [1182], 'channels': [1185, 1592, 1629, 1795, 2460, 2507, 2533, 2568], 'portal': [1188, 1255], 'myocytes.17,18': [1190], 'major': [1192, 1798], 'findings': [1193], 'exogenous': [1196, 1311], 'activity,': [1208, 1345], 'endogenous': [1213, 1275, 1320, 1342, 1433, 1437], 'agonists': [1220], '(platelet-derived': [1221], '[PDGF]': [1224], 'II)': [1227], 'isoform-dependent': [1231], 'B).': [1235], 'mediated': [1243], 'freshly': [1252], 'isolated': [1253], 'veins': [1256], 'express': [1258], 'p110γ,': [1261], 'p110β)': [1264], 'reconstituted': [1267], 'induction': [1273], 'expression.': [1277], 'previous': [1280, 1452], 'identify': [1282, 1349, 1824], 'different': [1284, 1571], 'agonist': [1294], 'involves': [1298], 'β1γ3': [1299], '(released': [1301], 'G13),': [1303], 'PI3Kγ,': [1304, 2866], 'PKC.18–20': [1306], 'It': [1307], 'surprising': [1309], 'peptide-dependent': [1315], 'fails': [1323], 'link': [1325, 1679], 'functional': [1326], 'Angiotensin': [1336], 'devoid': [1340], 'numerous': [1347], '(or': [1355], 'transactivation': [1356], 'epidermal': [1358], 'receptors)': [1361], 'aortic': [1363], 'vascular': [1364, 1386, 1809, 2424, 2462, 2504], 'tissues.': [1365], 'theory,': [1367], 'these': [1368, 1395, 1785], 'mechanisms': [1369, 1492, 1753], 'could': [1370], 'support': [1371], 'beds': [1387], 'may': [1388, 1814], 'explain': [1389], 'selectivity': [1392], 'observed': [1393], 'studies.': [1396, 1789], 'failure': [1398], 'readily': [1406], 'attributable': [1407], 'known': [1411], 'upstream': [1412], 'molecules.': [1414], 'Indeed,': [1415], 'experiments': [1417], 'Macrez': [1419, 2401, 2448, 2499, 2964], 'et': [1420, 2734], 'al17': [1421], 'do': [1422], 'distinguish': [1424], 'whether': [1425], 'lesion': [1427], 'channel.': [1443], 'either': [1445], 'case,': [1446], 'structurally': [1456], 'homologous': [1457], 'perform': [1463], 'unique': [1464], 'functions,': [1465], 'changes': [1468], 'availability': [1473], 'calibrate': [1474], 'PI3K-dependent': [1475], 'signaling.7': [1476], 'remains': [1487], 'uncertain,': [1488], 'several': [1490], '(nonexclusive)': [1491], 'possible,': [1494], 'including': [1495], 'effects': [1497], 'modulate': [1501], 'gating,': [1503], 'phosphorylation/activation': [1509], 'PKC': [1512], 'isoform,': [1513], 'analogous': [1516], 'leading': [1518], '(particularly': [1524], 'neurons21).': [1536], 'Finally,': [1537], 'there': [1538], 'no': [1540], 'reason': [1541], 'exclude': [1543], 'additional': [1551, 1670, 1752], 'might': [1554], 'regulate': [1555, 1726], 'activity.One': [1558], 'interesting': [1562], 'mechanistic': [1563], 'questions': [1564], 'raised': [1565], 'how': [1570], 'stimuli': [1573], 'PI3-kinase': [1578, 1589], 'One': [1580], 'obvious': [1581], 'potential': [1582], 'differential': [1585, 1625], 'compartmentalization': [1586], 'receptors,': [1588], 'isoforms,': [1590], 'and/or': [1591], 'subdomains.': [1595], 'appealing,': [1599], 'given': [1600], 'literature': [1602], 'describing': [1603], 'rafts': [1605], '(membrane': [1606], 'subdomains': [1607], 'particularly': [1608], 'enriched': [1609], 'lipids)': [1612], 'nucleation': [1614], 'centers': [1615], 'pathways.': [1618], 'Although': [1619], 'channels,': [1624], 'partitioning': [1626], 'potassium': [1628, 2567], 'raft': [1632], 'microdomains': [1633], 'proposed': [1636], 'ensure': [1641], 'efficient': [1642], 'phosphatases.22': [1647], 'presence': [1649], 'three': [1651], 'p110': [1655], 'complexes': [1660], 'any': [1662], 'seven': [1664], 'provides': [1668], 'independently': [1675], 'regulatable': [1676], 'cassettes': [1677], 'signaling.': [1684, 2609], 'versatility': [1686], 'dictating': [1696], 'composition': [1699], 'hence': [1701], 'function)': [1705], 'emphasized': [1710], 'only': [1715], 'holoenzymes': [1717], 'long': [1720], 'actin': [1728], 'cytoskeleton;': [1729], 'motifs': [1733], 'DNA': [1738], 'synthesis': [1739], 'less': [1741], 'spatially': [1742], 'organized': [1743], 'process23).': 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