The hVps34‐ <scp>SGK</scp> 3 pathway alleviates sustained PI3K/Akt inhibition by stimulating <scp>mTORC</scp> 1 and tumour growth

Name: Work Video:
Duration: 3 min 30 s
Ružica Bago; Eeva Sommer; Pau Castel; Claire Crafter; Fiona P. Bailey; Natalia Shpiro; José Baselga; Darren A.E. Cross; Patrick A. Eyers; Dario R. Alessi
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'PI3K/Akt': [12, 626, 748, 810, 831, 885, 897, 1063, 1768, 1877, 1908, 3136, 3511], 'inhibition': [13, 627, 829, 882, 1765, 1905, 2981, 3134, 3509], 'by': [14, 45, 71, 96, 115, 140, 166, 191, 210, 236, 267, 295, 321, 346, 365, 390, 416, 441, 460, 486, 517, 628, 721, 738, 755, 809, 911, 936, 944, 1179, 1230, 1265, 1335, 1366, 1443, 1466, 1647, 1724, 1736, 1754, 1783, 1826, 1901, 2038, 2100, 2207, 2283, 2423, 2555, 2579, 2674, 2765, 2920, 3063, 3076, 3133, 3139, 3209, 3267, 3307, 3508, 3514, 3571, 3622, 3663, 3753, 3796, 3820, 3893, 3902, 3931, 4004, 4016, 4193, 4215, 4305, 4317, 4348], 'stimulating': [15, 629, 948], 'mTORC1': [16, 630, 878, 949, 1779, 3845, 3864], 'and': [17, 29, 55, 80, 150, 175, 251, 279, 305, 330, 400, 425, 501, 543, 551, 565, 631, 641, 659, 703, 736, 771, 775, 782, 821, 842, 864, 901, 932, 950, 958, 995, 1000, 1057, 1082, 1091, 1117, 1125, 1277, 1295, 1324, 1378, 1434, 1458, 1463, 1507, 1522, 1563, 1642, 1652, 1677, 1702, 1716, 1752, 1775, 1780, 1820, 1828, 1841, 1923, 1936, 1953, 1975, 1997, 2010, 2036, 2151, 2171, 2223, 2255, 2293, 2295, 2326, 2358, 2375, 2388, 2417, 2431, 2438, 2534, 2631, 2645, 2726, 2743, 2745, 2749, 2760, 2784, 2792, 2819, 2853, 2892, 2935, 2948, 2998, 3047, 3058, 3118, 3141, 3154, 3260, 3303, 3382, 3405, 3458, 3482, 3527, 3615, 3658, 3767, 3846, 3852, 3889, 3907, 3928, 3952, 3973, 3989, 4009, 4025, 4128, 4213, 4221, 4246, 4278, 4300, 4326, 4405, 4419, 4427, 4444, 4460], 'tumour': [18, 632, 953, 1849], 'growth': [19], 'Ruzica': [20, 24, 270, 274, 522], 'Bago': [21, 25, 271, 275, 523, 1314, 1559, 1612], 'Corresponding': [22, 242, 272, 492], 'Author': [23, 243, 273, 493, 520], 'MRC': [26, 52, 147, 248, 276, 302, 397, 498], 'Protein': [27, 53, 148, 249, 277, 303, 398, 499, 549], 'Phosphorylation': [28, 54, 149, 250, 278, 304, 399, 500, 550], 'Ubiquitylation': [30, 56, 151, 252, 280, 306, 401, 502, 552], 'Unit,': [31, 57, 152, 253, 281, 307, 402, 503, 553], 'College': [32, 58, 153, 254, 282, 308, 403, 504, 554], 'of': [33, 37, 59, 63, 125, 128, 132, 154, 158, 221, 224, 228, 255, 259, 283, 287, 309, 313, 375, 378, 382, 404, 408, 471, 474, 478, 505, 509, 555, 559, 586, 589, 593, 638, 648, 690, 705, 732, 746, 780, 788, 804, 817, 830, 838, 883, 890, 903, 934, 956, 968, 983, 991, 998, 1042, 1048, 1060, 1071, 1096, 1100, 1183, 1208, 1214, 1236, 1275, 1362, 1471, 1475, 1478, 1499, 1536, 1600, 1604, 1628, 1650, 1668, 1689, 1699, 1705, 1748, 1766, 1778, 1811, 1838, 1848, 1869, 1885, 1906, 1918, 1929, 1944, 1947, 1959, 1986, 2034, 2060, 2083, 2130, 2166, 2313, 2355, 2414, 2435, 2488, 2558, 2566, 2637, 2732, 2768, 2850, 2865, 2871, 2917, 2945, 2982, 3010, 3091, 3135, 3169, 3190, 3202, 3251, 3270, 3278, 3365, 3428, 3444, 3510, 3542, 3552, 3564, 3604, 3606, 3625, 3633, 3676, 3679, 3683, 3692, 3702, 3722, 3744, 3765, 3769, 3786, 3803, 3817, 3833, 3891, 3909, 3996, 4007, 4012, 4019, 4036, 4047, 4059, 4067, 4099, 4116, 4121, 4151, 4160, 4165, 4173, 4181, 4191, 4198, 4209, 4285, 4294, 4307, 4319, 4350, 4375, 4383, 4393, 4409, 4441, 4455, 4476], 'Life': [34, 60, 155, 256, 284, 310, 405, 506, 556], 'Sciences,': [35, 61, 156, 257, 285, 311, 406, 507, 557], 'University': [36, 62, 131, 157, 227, 258, 286, 312, 381, 407, 477, 508, 558, 592], 'Dundee,': [38, 39, 64, 65, 159, 160, 260, 261, 288, 289, 314, 315, 409, 410, 510, 511, 560, 561], 'UK': [40, 66, 110, 135, 161, 205, 231, 262, 290, 316, 360, 385, 411, 455, 481, 512, 562, 584, 596], 'Search': [41, 67, 92, 111, 136, 162, 187, 206, 232, 263, 291, 317, 342, 361, 386, 412, 437, 456, 482, 513], 'for': [42, 68, 93, 112, 137, 163, 188, 207, 233, 264, 292, 318, 343, 362, 387, 413, 438, 457, 483, 514, 618, 753, 942, 1773, 1926, 1981, 2185, 2251, 2268, 2340, 2345, 2381, 2511, 2596, 2604, 2609, 2652, 2714, 2930, 2939, 2973, 3097, 3151, 3195, 3219, 3298, 3332, 3373, 3400, 3432, 3452, 3476, 3524, 3557, 3581, 3653, 3962, 4179], 'more': [43, 69, 94, 113, 138, 164, 189, 208, 234, 265, 293, 319, 344, 363, 388, 414, 439, 458, 484, 515, 1525, 2442], 'papers': [44, 70, 95, 114, 139, 165, 190, 209, 235, 266, 294, 320, 345, 364, 389, 415, 440, 459, 485, 516], 'this': [46, 72, 97, 116, 141, 167, 192, 211, 237, 268, 296, 322, 347, 366, 391, 417, 442, 461, 487, 518, 619, 872, 1511, 2087, 2318, 2341, 2605, 2621, 2812, 3498, 3874, 3979, 4423], 'author': [47, 73, 98, 117, 142, 168, 193, 212, 238, 269, 297, 323, 348, 367, 392, 418, 443, 462, 488, 519, 660], 'Eeva': [48, 50, 298, 300, 525], 'Sommer': [49, 51, 299, 301], 'Pau': [74, 76, 324, 326, 527], 'Castel': [75, 77, 325, 327], 'Human': [78, 173, 328, 423], 'Oncology': [79, 103, 174, 198, 329, 353, 424, 448, 564], 'Pathogenesis': [81, 176, 331, 426, 566], 'Program,': [82, 177, 332, 427, 567], 'Memorial': [83, 178, 333, 428, 568], 'Sloan': [84, 179, 334, 429, 569], 'Kettering': [85, 180, 335, 430, 570], 'Cancer': [86, 181, 336, 431, 571], 'Center,': [87, 182, 337, 432, 572], 'New': [88, 183, 338, 433, 573], 'York,': [89, 184, 339, 434, 574], 'NY,': [90, 185, 340, 435, 575], 'USA': [91, 186, 341, 436, 576], 'Claire': [99, 101, 349, 351, 529], 'Crafter': [100, 102, 350, 352], 'iMED,': [104, 199, 354, 449, 578], 'AstraZeneca,': [105, 200, 355, 450, 579], 'CRUK': [106, 201, 356, 451, 580], 'Cambridge': [107, 202, 357, 452, 581], 'Institute,': [108, 203, 358, 453, 582], 'Cambridge,': [109, 204, 359, 454, 583], 'Fiona': [118, 121, 368, 371, 531], 'P': [119, 122, 369, 372, 532], 'Bailey': [120, 123, 370, 373], 'Department': [124, 220, 374, 470], 'Biochemistry,': [126, 222, 376, 472, 587], 'Institute': [127, 223, 377, 473, 588], 'Integrative': [129, 225, 379, 475, 590], 'Biology,': [130, 226, 380, 476, 591], 'Liverpool,': [133, 134, 229, 230, 383, 384, 479, 480, 594, 595], 'Natalia': [143, 145, 393, 395, 534], 'Shpiro': [144, 146, 394, 396], 'José': [169, 171, 419, 421, 536], 'Baselga': [170, 172, 420, 422], 'Darren': [194, 196, 444, 446, 538], 'Cross': [195, 197, 445, 447], 'Patrick': [213, 216, 463, 466, 540], 'A': [214, 217, 464, 467, 541, 1220], 'Eyers': [215, 218, 465, 468], 'orcid.org/0000-0002-9220-2966': [219, 469], 'Dario': [239, 244, 489, 494, 544], 'R': [240, 245, 490, 495, 545], 'Alessi': [241, 246, 491, 496, 546], 'orcid.org/0000-0002-2140-9185': [247, 497], 'Information': [521], '1,': [524], 'Sommer1,': [526], 'Castel2,': [528], 'Crafter3,': [530], 'Bailey4,': [533], 'Shpiro1,': [535], 'Baselga2,': [537], 'Cross3,': [539], 'Eyers4': [542], '1': [547, 1131, 1982, 2178, 2182, 2261, 2265, 2347, 2382, 2498, 2501, 2504, 2508, 2657, 2660, 2663, 2667, 2940, 2994, 3079, 3098, 3101, 3148, 3156, 3196, 3224, 3227, 3230, 3234, 3252, 3366, 3370, 3429, 3453, 3521, 3529, 3558, 3585, 3589, 3963, 4321], '1MRC': [548], '2Human': [563], '3Oncology': [577], '4Department': [585], '*Corresponding': [597, 605], 'author.': [598, 606], 'Tel:': [599, 607], '+44': [600, 608], '1382385602;': [601, 609], 'E-mail:': [602, 610], '[email': [603, 611], 'protected]': [604, 612], 'EMBO': [614], 'Journal': [615], '(2016)35:1902-1922https://doi.org/10.15252/embj.201693929': [616], 'Correction(s)': [617], 'article': [620, 639], 'growth19': [633], 'October': [634], '2016': [635], 'PDFDownload': [636], 'PDF': [637], 'text': [640], 'main': [642], 'figures.': [643], 'Peer': [644], 'ReviewDownload': [645], 'a': [646, 706, 764, 778, 795, 825, 845, 867, 923, 959, 975, 1040, 1148, 1328, 1476, 1571, 1597, 1631, 1795, 1836, 1852, 1866, 1894, 2020, 2057, 2239, 2298, 2469, 2571, 2834, 2979, 3283, 3330, 3342, 3348, 3638, 3793, 4372, 4380], 'summary': [647], 'the': [649, 729, 801, 815, 818, 836, 874, 884, 904, 912, 937, 992, 1029, 1046, 1069, 1072, 1093, 1097, 1134, 1187, 1195, 1233, 1237, 1247, 1252, 1363, 1487, 1497, 1565, 1585, 1601, 1618, 1660, 1683, 1706, 1745, 1767, 1787, 1883, 1886, 1907, 1915, 1921, 1927, 2066, 2186, 2199, 2309, 2314, 2332, 2512, 2523, 2539, 2559, 2564, 2583, 2736, 2769, 2862, 2907, 3007, 3114, 3179, 3188, 3199, 3212, 3242, 3247, 3271, 3276, 3310, 3317, 3361, 3380, 3416, 3424, 3440, 3487, 3550, 3561, 3574, 3597, 3602, 3626, 3631, 3666, 3684, 3741, 3779, 3813, 3837, 3917, 4005, 4045, 4056, 4097, 4114, 4163, 4196, 4253, 4264, 4282, 4290, 4320, 4327, 4344, 4363, 4391, 4397, 4407, 4410, 4468], 'editorial': [650, 654], 'decision': [651, 655], 'including': [653, 1004, 1417, 1504], 'letters,': [656], 'reviewer': [657], 'comments': [658], 'responses': [661, 1261, 1297], 'to': [662, 665, 682, 700, 713, 728, 758, 827, 894, 928, 952, 1062, 1067, 1088, 1107, 1133, 1155, 1232, 1290, 1350, 1389, 1490, 1527, 1544, 1569, 1595, 1634, 1696, 1744, 1876, 1892, 1903, 1942, 2031, 2056, 2108, 2164, 2194, 2297, 2328, 2394, 2486, 2519, 2550, 2619, 2635, 2730, 2837, 2990, 3124, 3159, 3175, 3240, 3262, 3384, 3412, 3460, 3496, 3532, 3595, 3617, 3710, 3922, 3924, 3965, 4101, 4131, 4157, 4206, 4237, 4250, 4359], 'feedback.': [663], 'ToolsAdd': [664], 'favoritesDownload': [666], 'CitationsTrack': [667], 'CitationsPermissions': [668], 'ShareFacebookTwitterLinked': [669], 'InMendeleyWechatReddit': [670], 'Figures': [671], '&': [672, 1340, 1427, 3705], 'Info': [673], 'Abstract': [674], 'We': [675, 761, 1792, 4074, 4431], 'explore': [676, 2906, 3711], 'mechanisms': [677, 1044, 1059], 'that': [678, 710, 723, 766, 777, 917, 926, 1192, 1225, 1254, 1262, 1273, 1449, 1485, 1532, 1622, 1665, 1681, 1720, 1741, 1762, 1794, 1835, 1897, 1955, 2007, 2023, 2076, 2103, 2420, 2738, 2875, 2909, 3351, 3504, 3688, 3842, 3868, 3899, 3943, 3967, 4034, 4076, 4252, 4433, 4446], 'enable': [679], 'cancer': [680, 692, 791, 846, 860, 892, 971, 1013, 1299, 1480, 1671, 1861, 1949], 'cells': [681, 693, 861, 893, 1300, 1531, 1629, 1902, 2029, 2153, 2257, 2323, 2448, 2528, 2649, 2929, 2938, 2967, 3093, 3123, 3144, 3162, 3183, 3216, 3243, 3336, 3357, 3420, 3517, 3535, 3545, 3578, 3598, 3738, 3835, 3942, 4081, 4229, 4239], 'tolerate': [683], 'PI3K': [684, 695, 855, 1007, 1077, 1454, 1488, 1588, 1692, 1730, 1939, 2368, 2410, 2464, 2483, 2630, 2725, 2741, 2795, 2829, 2881, 3069, 3728], 'or': [685, 696, 856, 1626, 1693, 1731, 2120, 2181, 2202, 2264, 2273, 2311, 2446, 2465, 2507, 2666, 2830, 2882, 2959, 3027, 3070, 3084, 3106, 3233, 3249, 3347, 3363, 3369, 3426, 3442, 3448, 3588, 3729, 3826, 3882, 3998, 4263, 4287, 4292], 'Akt': [686, 697, 754, 781, 841, 857, 943, 957, 993, 999, 1124, 1152, 1173, 1209, 1255, 1379, 1415, 1491, 1528, 1684, 1694, 1732, 1774, 1839, 1922, 1935, 1968, 1996, 2026, 2049, 2067, 2078, 2104, 2141, 2161, 2400, 2466, 2632, 2727, 2746, 2791, 2831, 2883, 2924, 2970, 3040, 3071, 3191, 3553, 3730, 3772, 3827], 'inhibitors.': [687, 3731], 'Prolonged': [688, 1932, 2158, 2478, 2625, 2720], 'treatment': [689, 851, 1627, 1667, 1726, 1928, 1933, 2051, 2080, 2143, 2159, 2354, 2402, 2406, 2460, 2479, 2626, 2721, 2787, 2823, 2877, 2922, 3065, 3077, 3315, 3724, 3822], 'breast': [691, 790, 859, 891, 970, 1479, 1670, 1860, 1948], 'with': [694, 852, 1032, 1210, 1385, 1412, 1496, 1581, 1630, 1687, 1727, 1814, 1934, 1965, 2160, 2177, 2198, 2260, 2331, 2363, 2398, 2407, 2461, 2480, 2496, 2522, 2582, 2627, 2655, 2722, 2790, 2826, 2861, 2878, 2923, 2933, 2942, 2969, 2985, 3006, 3025, 3066, 3078, 3100, 3147, 3166, 3178, 3198, 3222, 3309, 3316, 3340, 3415, 3486, 3520, 3539, 3560, 3584, 3665, 3725, 3762, 3823, 3836, 3947, 3983, 4084, 4096, 4104, 4123, 4146, 4183, 4242, 4272, 4332, 4362, 4438, 4452], 'inhibitors': [698, 784, 858, 898, 997, 1064, 1492, 1529, 1688, 1714, 1733, 1844, 1940, 1969, 2105, 2162, 2369, 2411, 2467, 2484, 2633, 2728, 2747, 2796, 2832, 2884, 2977, 3072, 3829, 4385, 4415], 'leads': [699, 1695, 1941, 2030, 2163, 2485, 2634, 2729, 4130], 'increased': [701, 2032, 2885], 'expression': [702, 806, 900, 1498, 1871, 2082, 2133, 3354], 'activation': [704, 737, 772, 902, 908, 933, 990, 1704, 1722, 1753, 1777, 1825, 2731, 3675, 3701, 3890, 3908, 4035, 4066, 4139, 4159, 4190, 4214], 'kinase': [707, 915, 1130, 1568, 2553, 2754, 2763, 2843, 3052, 3265, 3387, 3463, 3620, 3687, 3808, 3828, 3859, 4301], 'termed': [708, 964, 1591, 1800], 'SGK3': [709, 718, 733, 751, 769, 905, 907, 921, 935, 940, 962, 1548, 1579, 1619, 1639, 1645, 1700, 1707, 1721, 1749, 1770, 1809, 1824, 1945, 2084, 2112, 2131, 2167, 2224, 2279, 2290, 2415, 2436, 2489, 2535, 2638, 2688, 2733, 2753, 2759, 2801, 2805, 2841, 2851, 2866, 2872, 2886, 2903, 2918, 3050, 3116, 3130, 3255, 3333, 3376, 3455, 3505, 3610, 3677, 3690, 3716, 3818, 3849, 3858, 3880, 3892, 3968, 4020, 4182, 4210, 4219, 4222, 4254, 4336, 4376, 4398, 4451], 'is': [711, 719, 909, 1065, 1084, 1174, 1271, 1398, 1446, 1564, 1734, 1890, 2003, 2019, 2813, 3137, 3512, 3790, 3900, 4094, 4140, 4144, 4371, 4480], 'related': [712], 'Akt.': [714, 1791], 'Under': [715], 'these': [716, 1033, 1049, 1514, 3122, 4232, 4394, 4434, 4447], 'conditions,': [717], 'controlled': [720, 910, 1264, 1735, 3791], 'hVps34': [722, 916, 1592, 1632, 1713, 2910, 2951, 3014, 3140, 3515, 3680, 3693, 3903, 3948], 'generates': [724, 918], 'PtdIns(3)P,': [725], 'which': [726, 1282, 1357, 1889, 3740, 3789, 3916, 4093, 4479], 'binds': [727, 927], 'PX': [730, 924, 1553, 1620, 1746, 4174, 4207], 'domain': [731, 925, 1235, 1554, 1574, 1621, 1747, 4175, 4208], 'promoting': [734, 930, 988], 'phosphorylation': [735, 931, 1178, 1204, 1213, 1229, 1354, 1361, 1649, 1751, 1985, 2012, 2033, 2147, 2390, 2428, 2557, 2767, 2852, 2895, 2984, 2989, 3041, 3044, 3061, 3119, 3269, 3624, 3719, 3774, 3785, 3816, 3854, 3881, 3888, 3906, 3927, 3930, 4018, 4212], 'its': [739, 1001, 1118, 1126, 1157, 1755, 3971, 4257], 'upstream': [740, 1002, 1127, 1756], 'PDK1': [741, 938, 1154, 1211, 1367, 1757, 1827, 3318, 3894, 3932, 3953, 4008, 4086, 4103, 4155, 4194, 4216, 4297, 4314, 4324], 'activator.': [742, 1758], 'Furthermore,': [743], 'under': [744, 2063, 2089, 3720, 4134], 'conditions': [745, 2064, 2090, 3721, 4135], 'prolonged': [747, 850, 1666, 1725, 1764, 2048, 2077, 2140, 2399, 2405, 2459, 2822, 2876, 2921, 3064, 3723, 3821], 'inhibition,': [750], 'substitutes': [752, 941], 'phosphorylating': [756, 945, 1467, 1784], 'TSC2': [757, 1785], 'activate': [759, 1486, 1682], 'mTORC1.': [760], 'characterise': [762], '14h,': [763, 4417], 'compound': [765, 3038], 'inhibits': [767, 1808, 3843], 'both': [768, 840, 1386, 1456, 1920, 2149, 2817, 2976, 3844], 'activity': [770, 879, 2027, 2764, 2802, 2844, 2854, 2904, 2916, 3032, 3053, 3117, 3131, 3506, 3809, 3860, 3883], 'in': [773, 794, 974, 1011, 1086, 1151, 1258, 1298, 1358, 1450, 1501, 1510, 1821, 1830, 1851, 1874, 2028, 2111, 2148, 2308, 2361, 2426, 2444, 2454, 2473, 2532, 2551, 2563, 2570, 2800, 2840, 2857, 2913, 3095, 3121, 3185, 3187, 3246, 3263, 3275, 3282, 3360, 3385, 3390, 3423, 3439, 3461, 3466, 3547, 3549, 3601, 3618, 3630, 3637, 3739, 3778, 3792, 3915, 3970, 3978, 4044, 4113, 4162, 4195, 4256, 4289, 4422], 'vivo,': [774], 'show': [776, 1761, 1834], 'combination': [779, 1837], 'SGK': [783, 843, 1377, 1546, 1842, 1924, 1998], 'induced': [785, 808, 1723, 1873, 2106, 2412, 2468, 2797, 2833, 2919, 2978, 3062, 3132, 3507, 3819], 'marked': [786, 1697, 1846], 'regression': [787, 967, 1847], 'BT-474': [789, 969, 1859], 'cell-derived': [792, 972], 'tumours': [793, 973, 985, 1451], 'xenograft': [796, 978, 1855], 'model.': [797, 979], 'Finally,': [798, 1863], 'we': [799, 1663, 1718, 1760, 1833, 1864, 2756, 2926, 3708, 3735, 3911, 4403], 'present': [800, 1661, 1865], 'kinome-wide': [802, 1867], 'analysis': [803, 1868, 2099, 2197, 2330, 2521, 2581, 2870, 3177, 3414, 4361], 'mRNA': [805, 1701, 1870, 2098, 2113, 2122, 2204, 2227, 2246, 2416, 2439, 2670, 2691, 2709], 'dynamics': [807, 1872], 'inhibition.': [811, 1879, 3334], 'Our': [812, 1880, 1911], 'findings': [813, 1881], 'highlight': [814, 1882], 'importance': [816, 1884], 'suggest': [822], 'it': [823], 'represents': [824], 'mechanism': [826, 870, 1896, 2810], 'counteract': [828, 1904], 'signalling.': [832], 'data': [834, 2336, 2600], 'support': [835], 'potential': [837, 1917], 'targeting': [839, 1919], 'as': [844, 1039, 1790, 1991, 1993, 2238, 2244, 2531, 2592, 2702, 2707, 2888, 2890, 3054, 3056, 3294, 3329, 3389, 3396, 3465, 3472, 3649, 3810, 3812, 3855, 3857], 'therapeutic.': [847], 'Synopsis': [848], 'Upon': [849], 'class': [853, 895], 'I': [854, 896, 1006, 1076, 1267, 1337, 1691, 1729, 1938, 2367, 2409, 2463, 2482, 2629, 2724, 2740, 2794, 2828, 2880, 3035, 3068, 3727, 3825], 'attain': [862], 'resistance': [863, 1036, 1061], 'proliferate.': [865], 'As': [866, 4390], 'novel': [868, 960], 'evasive': [869], 'explaining': [871], 'phenomenon,': [873], 'maintains': [877], 'following': [880, 1177, 1763], 'signalling': [886, 1685, 1909], 'pathway.': [887], 'Continuous': [888], 'exposure': [889, 4088], 'increases': [899, 2849], 'kinase.': [906, 939, 1709], 'endosomal': [913, 1640], 'lipid': [914, 3984, 4273], '3-phosphoinositide': [919], '[PI(3)P].': [920], 'possesses': [922, 1549], 'PI(3)P,': [929], 'TSC2,': [946], 'thereby': [947], 'leading': [951], 'progression.': [954], 'Combination': [955], 'selective': [961, 2947], 'inhibitor': [963, 1633, 1799, 2006, 2022, 2050, 2079, 2142, 2316, 2401, 2971, 3012, 3192, 3319, 3554, 3840, 3866, 3954, 4325, 4374, 4466], '14h': [965, 1801, 4370, 4465], 'induces': [966, 1147], 'nude': [976, 1853], 'mouse': [977, 1854], 'Introduction': [980], 'majority': [982], 'human': [984], 'harbour': [986], 'mutations': [987, 1484, 1680], 'inappropriate': [989], 'kinase,': [994], 'therefore,': [996], 'activators': [1003], 'Class': [1005, 1075, 1266, 1336, 1586, 1690, 1728, 1937, 2366, 2408, 2462, 2481, 2628, 2723, 2739, 2793, 2827, 2879, 2898, 3034, 3067, 3726, 3824], 'are': [1008, 1263, 1332, 1440, 1523, 2242, 2337, 2590, 2601, 2705, 3292, 3394, 3470, 3647], 'being': [1009], 'evaluated': [1010, 4406], 'many': [1012], 'clinical': [1014], 'trials': [1015], '(Liu': [1016, 1242], 'et': [1017, 1021, 1025, 1052, 1111, 1143, 1162, 1166, 1170, 1200, 1217, 1243, 1302, 1306, 1311, 1315, 1319, 1344, 1369, 1373, 1404, 1408, 1422, 1431, 1437, 1539, 1556, 1560, 1576, 1607, 1613, 1656, 1803, 1962, 1972, 1978, 2014, 2043, 2372, 2378, 2774, 2956, 2962, 3016, 3020, 3322, 3747, 3934, 3959, 4108, 4186, 4387], 'al,': [1018, 1022, 1026, 1053, 1112, 1144, 1163, 1167, 1171, 1201, 1218, 1244, 1303, 1307, 1312, 1316, 1320, 1345, 1370, 1374, 1405, 1409, 1423, 1432, 1438, 1540, 1557, 1561, 1577, 1608, 1614, 1657, 1804, 1963, 1973, 1979, 2015, 2044, 2373, 2379, 2775, 2957, 2963, 3017, 3021, 3323, 3748, 3935, 3960, 4109, 4187, 4388], '2009;': [1019, 1304], 'Vanhaesebroeck': [1020], '2012;': [1023], 'Bauer': [1024], '2015).': [1027, 1245, 4389], 'Despite': [1028], 'benefit': [1030], 'observed': [1031, 2397, 2856, 4043, 4141], 'molecules,': [1034], 'drug': [1035], 'can': [1037, 1898], 'emerge': [1038], 'result': [1041], 'adaptive': [1043], 'limiting': [1045], 'use': [1047], 'therapies': [1050], '(Rodon': [1051], '2013).': [1054, 1541], 'Therefore,': [1055, 4111], 'understanding': [1056], 'reverting': [1058], 'expected': [1066], 'improve': [1068], 'success': [1070], 'treatment.': [1073], 'family': [1078, 1589], '(p110α,': [1079], 'p110β,': [1080], 'p110γ': [1081], 'p110δ)': [1083], 'activated': [1085, 1176, 1334, 1453], 'response': [1087, 1875], 'extracellular': [1089], 'stimuli': [1090], 'phosphorylates': [1092, 1593, 3689], '3′-hydroxyl': [1094], 'group': [1095, 1477], 'inositol': [1098], 'moiety': [1099], 'membrane': [1101, 1136], 'bound': [1102], 'phosphatidylinositol': [1103], '4,5-bisphosphate': [1104], '(PtdIns': [1105], '(4,5)P2)': [1106], 'generate': [1108, 1596], 'PtdIns(3,4,5)P3': [1109, 1116, 1226], '(Vanhaesebroeck': [1110], '2001;': [1113, 1371, 1558], 'Cantley,': [1114], '2002).': [1115], 'immediate': [1119], 'breakdown': [1120], 'product': [1121], 'PtdIns(3,4)P2': [1122], 'recruit': [1123], 'regulator': [1128], 'phosphoinositide-dependent': [1129], '(PDK1)': [1132], 'plasma': [1135], 'via': [1137, 1355], 'their': [1138, 1287, 1348], 'PtdIns(3,4,5)P3/PtdIns(3,4)P2-binding': [1139], 'PH': [1140, 1234, 1329], 'domains': [1141, 1289], '(Mora': [1142], '2004).': [1145], 'This': [1146], 'conformational': [1149], 'change': [1150], 'enabling': [1153], 'phosphorylate': [1156, 1390], 'T-loop': [1158, 1364, 1651, 2891, 3057, 3853], 'Thr308': [1159, 1215, 2009, 2035], 'residue': [1160, 1191, 1365, 4176], '(Alessi': [1161, 1403], '1997a,b;': [1164], 'Stokoe': [1165], '1997;': [1168], 'Stephens': [1169], '1998).': [1172], 'fully': [1175], 'mTORC2': [1180, 1238, 1829, 3142, 3673, 3699, 3713, 3745, 3770, 3847, 3872, 3926], '(mammalian': [1181], 'target': [1182], 'rapamycin': [1184, 3451, 3867], 'complex-2)': [1185], 'at': [1186, 1786, 2993, 3000, 3873, 4021, 4027, 4055, 4312, 4342], 'hydrophobic': [1188, 1352, 1653, 2893, 3059, 3685, 3717, 3814, 3850, 3918], 'motif': [1189, 1353, 2894, 3060, 3686, 3718, 3815, 3851, 3919], 'Ser473': [1190, 1203, 1228, 2011, 2037, 3773], 'lies': [1193], 'within': [1194, 1286, 1394, 1617], 'C-terminal': [1196], 'non-catalytic': [1197], 'region': [1198], '(Sarbassov': [1199, 3746], '2005).': [1202, 1376, 1410], 'also': [1205, 1292, 1643, 1806, 2384, 3074, 3112, 3410, 3661, 3714, 3805, 4449], 'promotes': [1206, 1750, 3887, 4211], 'interaction': [1207, 1573, 4180], 'enhancing': [1212, 2145], '(Najafov': [1216, 3321, 3958], '2012).': [1219, 2045], 'recent': [1221], 'study': [1222, 2735, 4424], 'has': [1223, 1249, 1493, 3694], 'suggested': [1224], 'stimulates': [1227], 'binding': [1231, 1625, 1743, 4205], 'complex': [1239], 'Sin1': [1240], 'subunit': [1241, 3743], 'Although': [1246, 1322], 'focus': [1248], 'been': [1250, 1494, 3696, 3945], 'on': [1251, 2214, 2681, 2752, 3879], 'role': [1253, 2908], 'isoforms': [1256, 1274, 1326], 'play': [1257, 2912], 'mediating': [1259], 'proliferation': [1260, 1294, 1465], 'PI3Ks,': [1268], 'increasing': [1269, 2943, 3167, 3540, 3994], 'evidence': [1270, 3503], 'accumulating': [1272], 'serum': [1276, 2362, 3096, 3186, 3548], 'glucocorticoid': [1278], 'regulated': [1279, 3138, 3513], 'kinases': [1280, 1380, 1925], '(SGK)': [1281], 'share': [1283], '~50%': [1284], 'identity': [1285, 3682], 'catalytic': [1288, 2021, 3839], 'Akt,': [1291], 'control': [1293, 2299, 3126, 3331, 3343, 4070], 'survival': [1296], '(Vasudevan': [1301], 'Bruhn': [1305], '2010,': [1308], '2013;': [1309], 'Pearce': [1310], '2010;': [1313], '2014;': [1317, 3018], 'Gasser': [1318], '2014).': [1321, 1615, 1658, 2776, 2964, 3022], 'SGK1': [1323, 1500, 1520, 1537, 1798, 1819, 1960, 2092, 2119, 3703, 4384, 4414, 4437], 'SGK2': [1325, 2121, 2222], 'lack': [1327], 'domain,': [1330], 'they': [1331], 'still': [1333], 'PI3Ks': [1338], '(Kobayashi': [1339, 1426], 'Cohen,': [1341, 1428], '1999;': [1342, 1429], 'Kobayashi': [1343], '1999)': [1346], 'through': [1347], 'ability': [1349, 4098], 'induce': [1351, 1845], 'mTORC2,': [1356], 'turn': [1359], 'triggers': [1360], '(Biondi': [1368, 3933, 4107], 'Collins': [1372], '2003,': [1375], 'possess': [1381, 1570], 'similar': [1382, 2470], 'substrate': [1383, 2068, 2561, 2771, 3273, 3628], 'specificities': [1384], 'enzymes': [1387], 'preferring': [1388], 'Ser/Thr': [1391], 'residues': [1392], 'lying': [1393], 'Arg-Xaa-Arg-Xaa-Xaa-Ser/Thr': [1395], '(where': [1396], 'Xaa': [1397], 'any': [1399], 'amino': [1400], 'acid)': [1401], 'motifs': [1402, 1654], '1996;': [1406], 'Murray': [1407], 'Consistent': [1411, 3761], 'this,': [1413, 3734], 'several': [1414, 1669], 'substrates': [1416], 'FOXO': [1418], 'transcription': [1419], 'factors': [1420], '(Brunet': [1421], '2001),': [1424], 'GSK3': [1425], 'Dai': [1430], '2002)': [1433], 'NDRG1': [1435, 1994, 2061, 2146, 2387, 2427, 2474, 2983, 2988, 4026], '(Sommer': [1436, 1538, 1961], '2013)': [1439, 1964], 'similarly': [1441], 'phosphorylated': [1442], 'SGK1.': [1444], 'It': [1445], 'therefore': [1447], 'likely': [1448, 1891], 'displaying': [1452, 4473], 'signalling,': [1455], 'Akt1/2': [1457], 'SGK1/SGK2': [1459], 'would': [1460], 'be': [1461, 1899], 'elevated': [1462], 'stimulate': [1464], 'an': [1468, 1550, 2004, 2424, 2542, 3756, 4439, 4453, 4474], 'overlapping': [1469], 'subset': [1470], 'substrates.': [1472], 'sensitivity': [1474], 'cell': [1481, 1502, 1672, 1950, 2173, 2457, 2492, 2779, 3160, 3205, 3533, 3567], 'lines': [1482, 1503, 1515, 1673, 1951, 2174, 2493, 2780], 'possessing': [1483], 'correlated': [1495], 'ZR-75-1,': [1505, 2356], 'CAMA-1': [1506, 1954, 2152, 2172, 2256, 2357, 2447, 2642, 2820], 'T47D': [1508, 1676, 2359, 2450, 2646, 2858], '(utilised': [1509], 'study).': [1512], 'Interestingly,': [1513, 2128], 'all': [1516, 2455, 2778], 'contain': [1517], 'low': [1518, 1957], 'endogenous': [1519, 2758, 2915, 4085], 'levels': [1521, 1535, 1637, 1958, 2114, 2123, 2228, 2419, 2440, 2692, 2992, 4040, 4071], 'intrinsically': [1524], 'sensitive': [1526], 'than': [1530, 1818, 2449], 'express': [1533], 'higher': [1534, 1816, 3008], 'In': [1542, 1659, 2777, 2816, 2965, 3023], 'contrast': [1543], 'other': [1545], 'isoforms,': [1547], 'N-terminal': [1551], 'PtdIns(3)P-binding': [1552], '(Virbasius': [1555], '2014)': [1562, 2958], 'only': [1566, 4042], 'known': [1567], 'PtdIns(3)P': [1572, 1605, 1624, 1636, 1742, 3886, 3898, 3997, 4051, 4127, 4143, 4166, 4184, 4199, 4204, 4288], '(Pearce': [1575], '2010).': [1578], 'associates': [1580], 'endosome': [1582], 'membranes,': [1583], 'where': [1584, 2065, 2091, 4136], 'III': [1587, 2899], 'member': [1590], 'PtdIns': [1594, 4060, 4147, 4169, 4286], 'large': [1598], 'fraction': [1599], 'cellular': [1602], 'pool': [1603], '(Gillooly': [1606], '2000;': [1609], 'Backer,': [1610], '2008;': [1611], 'Mutations': [1616], 'ablate': [1623], 'reduce': [1635], 'blocked': [1638, 2139], 'localisation': [1641], 'suppressed': [1644, 2386, 3039, 3075, 3848, 4189], 'activity,': [1646, 2755, 3771], 'lowering': [1648], '(Bago': [1655, 2773, 2955, 3015, 4185], 'study,': [1662], 'demonstrate': [1664], '(ZR-75-1,': [1674, 2782], 'CAMA-1,': [1675], 'BT-474c)': [1678], 'harbouring': [1679], 'upregulation': [1698, 1943, 2165, 2413, 2487, 2636], 'subsequent': [1703], 'protein': [1708, 2085, 2132, 2418, 2437, 2762, 2806, 2842, 2887, 3051], 'Employing': [1710], 'structurally': [1711, 1966, 2364, 2949], 'diverse-specific': [1712], '(VPS34-IN1': [1715], 'SAR405),': [1717], 'establish': [1719], 'hVps34.': [1737], 'Mechanistic': [1738], 'studies': [1739, 4032], 'reveal': [1740], 'Moreover,': [1759, 1832], 'pathway,': [1769, 1888], 'could': [1771, 3904], 'substitute': [1772], 'promote': [1776, 3905, 3929], 'hence': [1781], 'S6K1': [1782], 'same': [1788], 'sites': [1789], 'discover': [1793], 'previously': [1796], 'reported': [1797], '(Halland': [1802, 4386], '2015)': [1805], 'potently': [1807], '(IC50': [1810], '4': [1812, 4477], 'nM)': [1813], '2.5-fold': [1815, 4481], 'potency': [1817, 3009, 4392], 'addition': [1822, 4006, 4306, 4318, 4349], 'blocks': [1823], 'cells.': [1831, 1862], '(MK-2206)': [1840, 2972], '(14h)': [1843], 'volume': [1850], 'model': [1856], 'derived': [1857], 'from': [1858, 2144, 2538, 3258, 3379, 3613, 3940, 4079, 4227], 'represent': [1893], 'major': [1895], 'used': [1900, 3328], 'network.': [1910], 'results': [1912], 'clearly': [1913], 'emphasise': [1914], 'therapeutic': [1916], 'cancer.': [1930], 'Results': [1931, 2241, 2704], 'Treatment': [1946, 3090, 3832], 'ZR-75-1': [1952, 2150, 2170, 2254, 2445, 2818, 2928, 2966, 3092, 3143, 3182, 3215, 3335, 3419, 3516, 3544, 3577, 3737, 3834], 'have': [1956], 'diverse': [1967, 2365, 2950], '(MK-2206': [1970, 2748], '(Hirai': [1971, 2013], '2010)': [1974], 'AZD5363': [1976, 2018, 2184, 2267], '(Davies': [1977, 2042], '2012))': [1980], 'h': [1983, 2383, 2941, 3099, 3157, 3197, 3530, 3559], 'inhibited': [1984, 4316, 4436], 'PRAS40': [1987, 2069, 2389, 3043], '(Thr246,': [1988], 'Akt-specific': [1989], 'substrate)': [1990, 1999], 'well': [1992, 2889, 3055, 3811, 3856], '(Thr346,': [1995], '(Fig': [2000, 2072, 2095, 2126, 2154, 2391, 2403, 2845, 2867, 2896, 2996, 3003, 3082, 3088, 3104, 3110, 3759, 3800, 3830, 3861, 3884, 4052, 4148, 4170, 4200, 4425, 4458], '1A).': [2001, 2073, 2096], 'MK-2206': [2002, 2180, 2263, 2934, 3150, 3368, 3431, 3523, 3587], 'allosteric': [2005], 'suppresses': [2008], '2010),': [2016], 'whereas': [2017, 2118, 3784], 'although': [2024], 'ablating': [2025], 'modulating': [2039], 'feedback': [2040], 'loops': [2041], 'Strikingly': [2046], 'however,': [2047], 'over': [2052, 2086], '1–10': [2053], 'days': [2054, 2654, 2932, 3153, 3221, 3583], 'led': [2055, 4156], 'time-dependent': [2058], 'recovery': [2059], 'phosphorylation,': [2062], 'remained': [2070, 2093], 'dephosphorylated': [2071, 3972, 4259], 'Immunoblotting': [2074], 'revealed': [2075, 2102, 4033], 'enhanced': [2081], 'period': [2088], 'undetectable': [2094], 'Quantitative': [2097], 'RT–PCR': [2101], '3-': [2107], '6-fold': [2109], 'increase': [2110, 2425, 2472, 2839], 'after': [2115], '2–10': [2116], 'days,': [2117, 2975, 3526], 'were': [2124, 2175, 2192, 2229, 2258, 2306, 2324, 2494, 2517, 2529, 2548, 2650, 2693, 3145, 3163, 3173, 3193, 3207, 3217, 3244, 3305, 3337, 3358, 3409, 3421, 3436, 3484, 3518, 3536, 3555, 3569, 3579, 3599, 3660, 4002, 4225, 4240, 4303, 4357], 'unaltered': [2125], '1B).': [2127], 'knockdown': [2129, 3764, 3782], 'employing': [2134, 3755], '3': [2135, 2456], 'distinct': [2136], 'shRNA': [2137, 2287, 2300, 3344, 3349, 3757, 3781], 'probes': [2138], '1C).': [2155], 'Figure': [2156, 2346, 2476, 2610, 2623, 3128, 3500, 4202], '1.': [2157], 'A,': [2168, 2291, 4217], 'B.': [2169, 4218], 'treated': [2176, 2259, 2495, 2530, 2651, 2927, 3146, 3165, 3194, 3218, 3438, 3519, 3538, 3556, 3580, 3946, 4241], 'μM': [2179, 2183, 2262, 2266, 2499, 2502, 2505, 2509, 2658, 2661, 2664, 2668, 2995, 3002, 3080, 3086, 3102, 3108, 3149, 3225, 3228, 3231, 3235, 3253, 3367, 3371, 3430, 3446, 3450, 3522, 3586, 3590, 3608, 4244, 4248, 4322], 'indicated': [2187, 2200, 2315, 2333, 2491, 2513, 2524, 2527, 2584, 3180, 3200, 3213, 3311, 3417, 3488, 3562, 3575, 3667, 4364], 'time': [2188], 'periods.': [2189], 'Cell': [2190, 2515, 3171], 'lysates': [2191, 2516, 2540, 3172, 3206, 3259, 3304, 3381, 3406, 3483, 3568, 3614, 3659], 'subjected': [2193, 2327, 2518, 2549, 3174, 3261, 3383, 3411, 3459, 3616, 4358], '(A)': [2195, 2533, 4262], 'immunoblot': [2196, 2329, 2520, 2580, 3176, 3210, 3308, 3413, 3572, 3664, 4360], 'antibodies': [2201, 2585], '(B)': [2203, 4269], 'isolation': [2205, 2671], 'followed': [2206, 2578, 2673], 'cDNA': [2208, 2215, 2675, 2682], 'preparation.': [2209, 2676], 'Real-time': [2210, 2677], 'PCR': [2211, 2678], 'was': [2212, 2280, 2396, 2421, 2441, 2536, 2672, 2679, 2855, 3073, 3256, 3327, 3377, 3456, 3611, 3750, 3775, 3798, 3920, 3938, 3969, 3981, 4014, 4041, 4072, 4082, 4255, 4270, 4315, 4330, 4346, 4400, 4467], 'performed': [2213, 2680], 'samples': [2216, 2237, 2683, 2701], 'using': [2217, 2231, 2235, 2284, 2541, 2684, 2695, 2699, 3211, 3573], 'specific': [2218, 2685, 3865], 'primers': [2219, 2686], 'against': [2220, 2687, 4471], 'SGK1,': [2221], 'isoforms.': [2225], 'Relative': [2226, 2690], 'calculated': [2230, 2694], '2(−ΔΔ)': [2232, 2696], 'Ct': [2233, 2697], 'method': [2234, 2698], 'DMSO-treated': [2236, 2700], 'calibrator.': [2240, 2703], 'presented': [2243, 2591, 2706, 3293, 3395, 3471, 3648], 'relative': [2245, 2708], 'level': [2247, 2710], 'means': [2248, 2593, 2711, 3295, 3397, 3473, 3650], '±': [2249, 2594, 2712, 3296, 3398, 3474, 3651], 'SD': [2250, 2595, 2713, 3297, 3399, 3475, 3652], 'triplicates.': [2252, 2715], 'C.': [2253], 'one': [2269], 'hour': [2270, 3238, 3593, 4235], '(1': [2271, 2788, 3325], 'h)': [2272, 2789], '10': [2274], 'days.': [2275, 3375, 3434], 'After': [2276, 4309, 4338], '7-day': [2277], 'treatment,': [2278], 'knocked': [2281], 'down': [2282, 3752], 'three': [2285], 'different': [2286], 'probes,': [2288], 'named': [2289, 2302], 'B': [2292], 'C': [2294], 'compared': [2296], 'probe,': [2301], 'sh': [2303], 'scramble.': [2304], 'Cells': [2305, 3435], 'maintained': [2307], 'presence': [2310, 2565, 3248, 3277, 3362, 3427, 3443, 3603, 3632, 4046, 4164, 4197, 4291], 'absence': [2312, 3189, 3250, 3364, 3425, 3441, 3551, 3605, 4115, 4293], 'during': [2317], 'period.': [2319], 'At': [2320], 'day': [2321], '10,': [2322], 'lysed': [2325], 'antibodies.': [2334, 2525, 3181, 3214, 3312, 3418, 3489, 3576, 3668, 4365], 'available': [2338, 2602], 'online': [2339, 2603], 'figure.': [2342, 2606, 2622, 3499], 'Data': [2344, 2608], '[embj201693929-sup-0003-SDataFig1.pdf]': [2348], 'Download': [2349, 2351, 2613, 2615, 2716, 2718, 3490, 3492, 3669, 3671, 4366, 4368], 'figure': [2350, 2614, 2717, 3491, 3670, 4367], 'PowerPoint': [2352, 2616, 2719, 3493, 3672, 4369], 'Similarly,': [2353], 'cultured': [2360, 3094, 3184, 3422, 3546], 'GDC0941': [2370, 2506, 2665, 3232, 3372], '(Folkes': [2371], '2008)': [2374], 'BKM120': [2376, 2510], '(Bendell': [2377], '2012)': [2380], 'markedly': [2385, 3776], '2A).': [2392, 2868], 'Analogous': [2393], 'what': [2395], '2A),': [2404], 'accompanied': [2422], '(Figs': [2429, 3045], '2A': [2430], 'EV1).': [2432], 'induction': [2434, 2864], 'pronounced': [2443], 'cells,': [2451, 2821, 2859, 3783], 'but': [2452, 4167], 'nevertheless': [2453], 'lines,': [2458], 'significant': [2471, 4065], 'phosphorylation.': [2475], '2.': [2477], 'either': [2497, 2656, 3223, 3341, 3993], 'MK-2206,': [2500, 2659, 3226], 'AZD5363,': [2503, 2662, 3229], 'times.': [2514], 'immunoprecipitated': [2537, 2757, 3257, 3378, 3457, 3612], 'anti-SGK3': [2543], 'antibody.': [2544], 'immunoprecipitates': [2546, 2873, 3480], '(IP)': [2547, 3302, 3404, 3481, 3657], 'vitro': [2552, 3264, 3386, 3462, 3619], 'assay': [2554, 3266, 3388, 3464, 3621], 'measuring': [2556, 2766, 3268, 3623], 'Crosstide': [2560, 2770, 3272, 3627], 'peptide': [2562, 2772, 3274, 3629], '0.1': [2567, 3279, 3445, 3449, 3634], 'mM': [2568, 3280, 3635], '[γ-32P]ATP': [2569, 3281, 3636], '30': [2572, 3284, 3639, 4310, 4340], 'min': [2573, 3285, 3640, 4311, 4341], '30°C': [2574, 3286, 3641], 'reaction': [2575, 3287, 3642, 4328, 4345, 4355], '(upper': [2576, 3288, 3643], 'panel)': [2577, 2644, 2648, 3408], '(lower': [2586, 3407], 'panel).': [2587, 3289, 3644], 'Kinase': [2588, 3290, 3392, 3468, 3645, 4000], 'reactions': [2589, 3291, 3393, 3469, 3646, 4001, 4302], 'triplicate': [2597, 3299, 3401, 3477, 3654], 'reaction.': [2598, 3300, 3402, 3478, 3655], '2': [2611, 4333], '[embj201693929-sup-0004-SDataFig2.pdf]': [2612], 'Click': [2617, 3494], 'here': [2618, 3495], 'expand': [2620, 3497], 'EV1.': [2624], 'mRNAZR-75-1': [2639], '(left': [2640], 'panel),': [2641], '(middle': [2643], '(right': [2647], '5': [2653, 2931, 2974, 3152, 3220, 3374, 3433, 3525, 3582, 3950, 3956, 4243, 4247], 'BKM120.': [2669, 3236], 'isoform.': [2689], 'To': [2734, 2905, 3732, 3895], 'effect': [2737, 3878], '(GDC0941': [2742], 'BKM120)': [2744], 'AZD5363)': [2750], 'had': [2751, 3876, 3944], 'assessed': [2761, 4015], 'tested': [2781, 4061], 'CAMA1': [2783], 'T47D),': [2785], 'short-term': [2786], 'transient': [2798], 'reduction': [2799], 'without': [2803], 'affecting': [2804], 'levels.': [2807, 3127], 'underlying': [2809], 'behind': [2811], 'not': [2814, 3695, 3870, 4168, 4401], 'clear.': [2815], '(5': [2824], 'days)': [2825], 'robust': [2835], '2-': [2836], '4-fold': [2838], '2B).': [2846, 2897], 'More': [2847], 'moderate': [2848], 'consistent': [2860, 3005, 4095], 'lower': [2863], 'Immunoblot': [2869], 'confirmed': [2874, 4432], 'PI3K,': [2900, 3036], 'hVps34,': [2901], 'controls': [2902], 'might': [2911], 'regulating': [2914], 'inhibitors,': [2925, 2952], 'then': [2936, 3437], 'incubated': [2937, 3245, 3600, 3982, 4271], 'doses': [2944, 3168, 3541], 'highly': [2946], 'namely': [2953], 'VPS34-IN1': [2954, 2986, 3026, 3081, 3103, 4245], 'SAR405': [2960, 2999, 3011, 3028, 3087, 3109], '(Ronan': [2961], 'pre-treated': [2968], 'dose-dependent': [2980], 'reducing': [2987], 'basal': [2991, 3115], '3A)': [2997], '0.3': [3001, 3085, 3107, 3607], 'EV2A),': [3004], 'towards': [3013, 3033, 4396], 'Ronan': [3019], 'agreement': [3024], 'having': [3029], 'no': [3030, 3877, 4064, 4137], 'inhibitory': [3031], 'neither': [3037], 'nor': [3042], '3B': [3046], 'EV2B).': [3048], 'Elevated': [3049], '3C)': [3083, 3105], 'EV2C).': [3089], 'EV2C)': [3111], 'reduced': [3113, 3777], 'detected': [3120], 'below': [3125], '3.': [3129], 'then,': [3155, 3528], 'prior': [3158, 3239, 3531, 3594, 4236], 'lysis,': [3161, 3241, 3534, 3596, 4238], 'further': [3164, 3537, 4158], 'VPS34-IN1.': [3170, 3203, 3254], 'concentrations': [3201, 3563, 3995, 4284], 'analysed': [3208, 3306, 3485, 3570, 3662], 'One': [3237, 3592, 4234], 'Immunoprecipitates': [3301, 3403, 3656], 'One-hour': [3313], '(1-h)': [3314], 'GSK2334470': [3320, 4249, 4323], '2011)': [3324, 3961], 'μM)': [3326, 3951, 3957], 'stably': [3338], 'transfected': [3339], 'vector': [3345, 3350], '(scrambled)': [3346], 'targets': [3352], 'Rictor': [3353, 3742, 3766, 3780, 3804], '(shRictor).': [3355], 'grown': [3359], '(C).': [3391, 3467], 'AZD8055': [3447, 3841], 'h.': [3454], 'EV2.': [3501], 'Further': [3502], 'SAR405.': [3543, 3565, 3609], 'GDC0941.': [3591], 'regulates': [3674, 3700], 'downstream': [3678, 3691], 'established.': [3697], 'Since': [3698], '(Garcia-Martinez': [3704], 'Alessi,': [3706], '2008),': [3707], 'wished': [3709], 'whether': [3712, 3897], 'mediates': [3715], 'achieve': [3733], 'generated': [3736], '2005)': [3749], 'knock': [3751], '~90%': [3754], 'approach': [3758], '3D).': [3760, 3801, 3831], 'efficient': [3763], 'suppression': [3768], 'S6': [3787], 'protein,': [3788], 'Rictor-independent': [3794], 'manner': [3795, 3980], 'mTORC1,': [3797], 'unaffected': [3799], 'Knockdown': [3802], 'virtually': [3806], 'ablated': [3807], 'mTOR': [3838], '3E).': [3862, 3885], 'However,': [3863], 'does': [3869], 'inhibit': [3871], 'concentration': [3875, 4058], 'investigate': [3896], 'produced': [3901], 'SGK3,': [3910, 4472], 'utilised': [3912], 'recombinant': [3913, 4118, 4154, 4296], 'SGK3[S486E],': [3914], 'mutated': [3921], 'Glu': [3923], 'mimic': [3925], '2001).': [3936, 4110], 'SGK3[S486E]': [3937, 3976, 4013, 4037, 4068, 4077, 4100, 4122, 4161, 4192], 'purified': [3939, 3977, 4226], 'HEK293': [3941, 4080, 4228], '(VPS34-IN1,': [3949], '(GSK2334470,': [3955], 'h,': [3964], 'ensure': [3966, 4251], 'inactive': [3974, 4258], 'form.': [3975, 4260], 'vesicles': [3985, 4049, 4125, 4274], 'comprising': [3986, 4275], 'phosphatidylcholine': [3987, 4276], '(PC)': [3988, 4277], 'phosphatidylserine': [3990, 4279], '(PS)': [3991, 4280], 'containing': [3992, 4050, 4126, 4281], 'PtdIns.': [3999], 'initiated': [4003, 4304], 'MgATP.': [4010, 4308], 'Activation': [4011], 'monitoring': [4017], 'Thr320': [4022], '(PDK1': [4023], 'site)': [4024], 'Thr346': [4028], '(SGK1': [4029], 'site).': [4030], 'These': [4031], 'beyond': [4038, 4069], 'background': [4039], 'PS/PS': [4048], '4A).': [4053], 'Even': [4054], 'highest': [4057], '(10': [4062], 'μM),': [4063], 'observed.': [4073], 'found': [4075, 4445], 'isolated': [4078], 'contaminated': [4083], '(high': [4087], 'immunoblot,': [4089], 'see': [4090], 'Fig': [4091, 4429, 4462], '4),': [4092], 'bind': [4102], 'high': [4105], 'affinity': [4106], 'even': [4112], 'added': [4117, 4295], 'PDK1,': [4119], 'incubation': [4120], 'PC/PS': [4124], 'MgATP': [4129], 'partial': [4132], 'activation,': [4133], 'detectable': [4138], 'when': [4142], 'replaced': [4145], '4B).': [4149, 4171, 4201], 'Addition': [4150], '50': [4152], 'ng': [4153], 'Mutation': [4172], 'Arg90,': [4177], 'required': [4178], '2014),': [4188], '4.': [4203], '[S486E]-GST': [4220], '[R90A': [4223], 'S486]-GST': [4224], 'transiently': [4230], 'overexpressing': [4231], 'enzymes.': [4233], 'SGK3[S486E]-GST': [4261], 'non-PtdIns(3)P-binding': [4265], 'mutant': [4266], 'SGK3[R90A,': [4267], 'S486E]-GST': [4268], 'indicted': [4283], '(50': [4298], 'ng)': [4299], '30°C,': [4313, 4343], 'mixture': [4329], 'supplemented': [4331], 'μg': [4334], 'GST-NDRG1': [4335], 'substrate.': [4337], 'another': [4339], 'terminated': [4347], 'SDS': [4351], 'sample': [4352], 'buffer.': [4353], 'mixtures': [4356], 'potent': [4373, 4413, 4470], 'Recently,': [4377], 'Sanofi': [4378], 'published': [4379], 'new': [4381], 'series': [4382], 'compounds': [4395, 4435, 4448], 'isoform': [4399], 'reported,': [4402], 'synthesised': [4404], 'selectivity': [4408], 'four': [4411], 'most': [4412, 4469], '(14g,': [4416], '14i': [4418], '14n)': [4420], 'described': [4421], '5A': [4426], 'Appendix': [4428, 4461], 'S1A).': [4430], 'IC50': [4440, 4454, 4475], '10–70': [4442], 'nM': [4443, 4457], 'targeted': [4450], '4–80': [4456], '5B': [4459], 'S1B).': [4463], 'nM,': [4478], 'mo': [4482]}, 'cited_by_api_url': 'https://api.openalex.org/works?filter=cites:W2501576242', 'counts_by_year': [{'year': 2024, 'cited_by_count': 4}, {'year': 2023, 'cited_by_count': 8}, {'year': 2022, 'cited_by_count': 6}, {'year': 2021, 'cited_by_count': 14}, {'year': 2020, 'cited_by_count': 12}, {'year': 2019, 'cited_by_count': 14}, {'year': 2018, 'cited_by_count': 11}, {'year': 2017, 'cited_by_count': 10}, {'year': 2016, 'cited_by_count': 1}], 'updated_date': '2024-12-18T09:31:12.432887', 'created_date': '2016-08-23'}
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