Inhibition of Insulin Receptor Activation by Insulin-like Growth Factor Binding Proteins

Name: Work Video:
Duration: 3 min 30 s
Yoshitaka Yamanaka; Emily Wilson; Ron G. Rosenfeld; Youngman Oh
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2744, 2750, 2755, 2768, 2782, 2791, 2802, 2806, 2816, 2830, 2858, 2877, 2900, 2909, 2942, 3011, 3019, 3117, 3169, 3224, 3254, 3285, 3309, 3331, 3364, 3367, 3388, 3411, 3458, 3480, 3497, 3500, 3519, 3532, 3542, 3557, 3595, 3598, 3606, 3708, 3740, 3772, 3804, 3834, 3902, 3977, 3982, 3987, 4008, 4024, 4032, 4035, 4072, 4076, 4098, 4272, 4280, 4392, 4434, 4449, 4452], 'high-affinity': [11, 65, 180, 234, 2748], 'binding': [12, 22, 67, 72, 181, 191, 236, 241, 352, 475, 1170, 1636, 1726, 2199, 2557, 2577, 2613, 2672, 2692, 2701, 2724, 2739, 2749, 2757, 2829, 2849, 2864, 3047, 3171, 3217, 3249, 3287, 3292, 3330, 3363, 3369, 3395, 3524, 3586, 3999], 'proteins': [13, 182, 476, 579, 722, 2130, 2304, 2382, 2392, 2416, 3893, 4406], '(IGFBPs)': [14, 183, 477], 'that': [15, 46, 56, 100, 119, 184, 215, 225, 269, 288, 896, 1153, 2477, 2534, 2625, 2651, 2689, 2722, 2764, 2862, 2881, 2907, 2935, 3010, 3033, 3054, 3071, 3230, 3355, 3436, 3450, 3572, 3611, 3620, 3639, 3664, 3687, 3711, 3751, 3760, 3780, 3830, 4384], 'protect': [16, 185], 'IGFs': [17, 58, 186, 227, 424, 469, 584, 846, 853, 2457, 2634, 2661, 2685, 2711, 2751, 2771, 2833, 3197, 3618, 3622, 3854, 3898], 'from': [18, 187, 1194, 1292, 1344, 1359, 1476, 1494, 1511, 1543, 1558, 1615, 1628, 1899, 3430, 4421], 'degradation,': [19, 188], 'limit': [20, 189], 'their': [21, 190, 732, 855, 1401, 2547], 'to': [23, 37, 73, 155, 192, 206, 242, 324, 377, 471, 718, 738, 854, 1067, 1147, 1171, 1524, 1691, 1707, 1739, 1770, 1792, 1836, 1934, 1949, 1962, 2156, 2252, 2406, 2419, 2501, 2523, 2578, 2582, 2608, 2706, 2788, 2832, 2836, 2850, 2865, 3126, 3131, 3141, 3172, 3234, 3288, 3333, 3370, 3396, 3521, 3525, 3579, 3587, 3626, 3719, 3742, 3756, 4000, 4382, 4446], 'IGF': [24, 28, 193, 197, 351, 432, 728, 736, 2700, 2723, 2925, 2993, 3216, 4419, 4422, 4436], 'receptors,': [25, 194], 'and': [26, 77, 95, 143, 165, 195, 246, 264, 312, 334, 372, 390, 420, 481, 564, 586, 588, 730, 734, 1060, 1125, 1143, 1150, 1155, 1174, 1185, 1288, 1305, 1408, 1484, 1532, 1571, 1624, 1666, 1710, 1733, 1764, 1843, 1872, 1878, 1923, 1955, 1971, 2026, 2034, 2090, 2099, 2112, 2154, 2176, 2184, 2300, 2310, 2335, 2361, 2403, 2458, 2586, 2669, 2686, 2712, 2731, 2772, 2796, 2844, 2913, 2938, 2958, 3060, 3129, 3137, 3147, 3174, 3180, 3183, 3266, 3298, 3347, 3403, 3469, 3475, 3492, 3537, 3574, 3582, 3604, 3617, 3645, 3680, 3682, 3745, 3759, 3818, 3967, 3990, 4003, 4010, 4047, 4292, 4437, 4440, 4463, 4470], 'modulate': [27, 196, 1168], 'actions.': [29, 198], 'six': [31, 200, 542, 565], 'classical': [32, 201], 'IGFBPs': [33, 111, 147, 202, 280, 316, 545, 714, 1140, 2454, 2499, 2524, 2535, 2566, 2606, 2644, 2783, 2823, 2831, 2851, 2866, 2901, 2910, 3070, 3204, 3240, 3459, 3628, 3666, 3741, 3752, 3835, 3959, 3992, 4396, 4417], 'have': [34, 38, 203, 207, 546, 573, 894, 1064, 1151, 2707, 2720, 3576, 3623, 3637, 3716, 3736, 3753, 3778, 3828, 4020, 4091], 'been': [35, 204, 462, 1065, 2258, 3662, 4092], 'believed': [36, 205, 717], 'no': [39, 208], 'affinity': [40, 62, 108, 142, 150, 209, 231, 277, 311, 319, 480, 582, 844, 1760, 1931, 2452, 2461, 2544, 2622, 2642, 2709, 2767, 2776, 2889, 2923, 2928, 2955, 2960, 2991, 3000, 3029, 3048, 3074, 3080, 3195, 3200, 3215, 3263, 3268, 3379, 3410, 3448, 3653, 3728, 3765, 3852, 3896, 3969, 4399], 'for': [41, 112, 151, 210, 281, 320, 583, 723, 845, 1300, 1530, 1536, 1672, 1700, 1913, 1964, 2028, 2047, 2166, 2207, 2220, 2249, 2265, 2329, 2375, 2456, 2549, 2558, 2565, 2643, 2658, 2710, 2770, 2777, 2924, 2929, 2951, 2956, 2961, 2992, 3001, 3030, 3049, 3068, 3075, 3081, 3196, 3201, 3213, 3264, 3269, 3362, 3415, 3729, 3766, 3823, 3853, 3897, 3970, 4018, 4400, 4412, 4431, 4467, 4473], 'insulin.': [42, 211, 1788, 1815, 3050, 3289, 3365], 'We': [43, 212, 572, 1133, 3279, 3749, 4455], 'now': [44, 213], 'demonstrate': [45, 214, 3571, 3750], 'IGFBP-7/mac25,': [47, 216], 'newly': [49, 218], 'identified': [50, 219, 1882, 4085], 'member': [51, 220], 'the': [53, 74, 80, 90, 125, 156, 222, 243, 249, 259, 294, 325, 388, 429, 436, 468, 561, 569, 594, 695, 709, 1072, 1137, 1180, 1246, 1521, 1551, 1661, 1679, 1683, 1703, 1782, 1807, 1854, 1864, 1886, 1900, 1924, 1935, 1941, 1986, 2093, 2097, 2182, 2242, 2318, 2386, 2433, 2451, 2460, 2494, 2509, 2553, 2573, 2610, 2626, 2690, 2699, 2729, 2735, 2753, 2765, 2773, 2789, 2799, 2807, 2817, 2822, 2825, 2875, 2897, 2939, 2952, 2980, 2984, 2990, 2999, 3037, 3046, 3058, 3069, 3079, 3083, 3092, 3103, 3120, 3177, 3184, 3209, 3247, 3252, 3255, 3282, 3305, 3408, 3412, 3453, 3481, 3517, 3529, 3577, 3588, 3593, 3599, 3624, 3656, 3705, 3717, 3732, 3738, 3754, 3770, 3801, 3831, 3840, 3900, 3968, 3978, 3988, 4005, 4022, 4025, 4029, 4070, 4432, 4435, 4450], 'IGFBP': [54, 223, 595, 840, 1725, 2576, 2943, 3170, 3256, 3844, 3904], 'superfamily': [55, 224, 596, 3905], 'binds': [57, 138, 226, 307, 2479, 3438, 3642], 'specifically': [59, 228, 1165], 'with': [60, 140, 148, 229, 309, 317, 385, 478, 580, 842, 1410, 1590, 1655, 1885, 1940, 1957, 1975, 2083, 2115, 2140, 2172, 2187, 2241, 2260, 2338, 2395, 2427, 2465, 2474, 2526, 2541, 2546, 2588, 2780, 2880, 2915, 2979, 3009, 3021, 3133, 3143, 3359, 3446, 3490, 3630, 3648, 3796, 3850, 3894, 4015, 4106, 4397, 4409], 'low': [61, 230, 2766, 2954, 3199, 3895], 'is': [63, 102, 232, 271, 439, 2646, 2741, 2810, 2867, 3112, 3231, 3258, 3619, 3676, 4380], 'insulin': [66, 71, 75, 84, 91, 113, 139, 145, 152, 157, 235, 240, 244, 253, 260, 282, 308, 314, 321, 326, 355, 386, 437, 1076, 1116, 1149, 1164, 1169, 1181, 1356, 1491, 1553, 2177, 2244, 2480, 2539, 2632, 2663, 2691, 2713, 2863, 2930, 2957, 3002, 3173, 3202, 3235, 3248, 3265, 3326, 3336, 3360, 3368, 3394, 3439, 3454, 3461, 3482, 3523, 3581, 3585, 3589, 3600, 3616, 3672, 3679, 3721, 3744, 3747, 3773, 3795, 3808, 3971, 3998, 4278, 4287, 4294, 4386, 4410, 4438, 4453], 'protein.': [68, 106, 237, 275], 'IGFBP-7': [69, 101, 238, 270, 693, 1154, 1301, 1763, 1774, 1796, 2091, 2264, 2473, 2478, 2559, 2630, 2703, 2769, 2803, 2813, 3207, 3286, 3342, 3356, 3374, 3404, 3437, 3476, 3573, 3640, 4019], 'blocks': [70, 144, 239, 313], 'receptor': [76, 92, 245, 261, 356, 1173, 1182, 1554, 2245, 3291, 3462, 3467, 3483, 3601, 4002, 4009, 4288, 4295], 'thereby': [78, 247], 'inhibiting': [79, 248, 735, 909, 1176], 'earliest': [81, 250], 'steps': [82, 251], 'in': [83, 252, 387, 708, 839, 912, 1241, 1312, 1404, 1573, 1598, 1667, 1748, 1781, 1806, 1820, 1951, 1996, 2036, 2059, 2096, 2101, 2181, 2195, 2233, 2322, 2363, 2481, 2489, 2821, 2871, 2874, 2883, 2896, 2918, 2922, 2948, 2972, 2997, 3006, 3024, 3028, 3044, 3064, 3114, 3193, 3203, 3261, 3304, 3419, 3427, 3486, 3592, 3670, 3694, 3769, 3790, 3847, 4028, 4041, 4086, 4094], 'action,': [85, 254], 'such': [86, 255, 3465, 4402], 'as': [87, 256, 398, 400, 554, 720, 834, 1310, 1374, 1717, 1747, 1819, 1994, 2057, 2411, 2445, 2597, 2599, 2886, 3318, 3320, 3417, 3466, 3514, 3562, 3963, 3965, 4038, 4040, 4078, 4080, 4283, 4403, 4416], 'autophosphorylation': [88, 257, 1178, 3468, 3479, 3597], 'β': [93, 262, 1183, 3484, 3602], 'subunit': [94, 263, 1184, 3485, 3603], 'phosphorylation': [96, 265, 1186, 3531, 3605], 'IRS-1,': [98, 267, 354], 'indicating': [99, 268, 3354], 'functional': [104, 273], 'insulin-binding': [105, 274], 'other': [110, 166, 279, 335, 2611, 3657, 4081], 'can': [114, 283, 2785, 2852, 3219, 3357, 3960, 3972], 'be': [115, 284, 905, 1068, 2695, 2786, 2853, 3087, 3425, 3837, 3973], 'enhanced': [116, 149, 285, 318, 850, 1987, 4398], 'modifications': [118, 287], 'disrupt': [120, 289], 'disulfide': [121, 290, 2936, 3034, 3055, 3190, 3225, 3983], 'bonds': [122, 291, 2937, 3035, 3056, 3191, 3984], 'or': [123, 292, 1119, 1651, 1656, 1745, 1776, 1780, 1787, 1798, 1805, 1814, 1960, 2116, 2127, 2146, 2263, 2468, 2675, 2678, 2697, 3098, 3101, 3107, 3144, 3156, 3245, 3307, 3313, 3502, 3544, 3788, 3985, 4111, 4395], 'remove': [124, 293], 'conserved': [126, 295, 558, 566, 699, 2792, 3178], 'COOH': [127, 296, 712, 2800, 2985, 3061], 'terminus.': [128, 297, 571, 713, 2827], 'Like': [129, 298], 'IGFBP-7,': [130, 299, 1142, 2175, 3389, 3503, 3545], 'an': [131, 300, 913, 1909, 3903], 'NH2-terminal': [132, 301, 1156, 3179], 'fragment': [133, 302, 1157, 1860, 3039], 'IGFBP-3': [135, 304, 1059, 1061, 1124, 1144, 1159, 1232, 1777, 1802, 2659, 2674, 2736, 3013, 3084, 3136, 3402, 3444, 3508, 3520, 3698, 3713, 3762, 3781, 3805, 4393], '(IGFBP-3(1–87)),': [136, 305], 'also': [137, 306, 904, 1167, 2537, 3641], 'high': [141, 310, 479, 2775, 2959, 3073, 3194, 3214, 3319, 3631, 3798], 'action.': [146, 315, 3673, 3748, 3774, 3809], 'might': [153, 322, 3689, 4388], 'contribute': [154, 323], 'resistance': [158, 327, 4279, 4387], 'pregnancy,': [160, 329, 837], 'type': [161, 330, 430], 'II': [162, 331], 'diabetes': [163, 332, 4109, 4113], 'mellitus,': [164, 333, 4110], 'pathological': [167, 336], 'conditions.': [168, 337], 'Insulin-like': [338], '(IGFs)-I': [341], '1The': [342], 'abbreviations': [343], 'used': [344, 1535, 1835], 'are:': [345, 2631, 2660], 'IGF,': [346], 'factor;': [349], 'IGFBP,': [350], 'protein;': [353, 3989], 'substrate-1;': [357], 'PAGE,': [358], 'polyacrylamide': [359], 'gel': [360, 1538, 1954], 'electrophoresis;': [361], 'm.o.i.,': [362], 'multiplicity': [363], 'infection;': [365], 'WLB,': [366], 'Western': [367], 'ligand': [368], 'blot;': [369], 'DTT,': [370, 3146], 'dithiothreitol.': [371], '-II': [373], 'structurally': [375], 'related': [376, 3892], 'insulin,': [378, 467, 2255, 2459, 2579, 2687, 2778, 3031, 3082, 3311, 3416, 3709, 3758, 3767, 3962, 4401], 'sharing': [379], 'approximately': [380, 2561], '50%': [381], 'amino': [382, 562, 1850, 2793], 'acid': [383, 1851, 2794], 'homology': [384, 707], 'A-': [389], 'B-chain': [391], 'regions': [392, 2733], 'but': [393, 704, 1166, 2540, 2926, 3198, 3218, 3390, 3647, 3700, 4089], 'retaining': [394], 'connecting': [396], 'peptide,': [397], 'well': [399, 543, 2598, 3964, 4039, 4079], 'carboxyl-terminal': [402], 'extension': [403], '(1Daughaday': [404], 'W.': [405], 'Rotwein': [406], 'P.': [407, 602, 741, 1026, 1040, 1078, 2064, 4151, 4210, 4348, 4457], 'Endocr.': [408, 487], 'Rev.': [409, 450, 488, 4370], '1989;': [410, 808, 4371], '10:': [411], '68-91Crossref': [412], 'PubMed': [413, 455, 492, 536, 638, 661, 753, 772, 794, 811, 826, 874, 887, 948, 970, 992, 1014, 1032, 1052, 1090, 1105, 1225, 1278, 1336, 1391, 1433, 1463, 2013, 2078, 3872, 3885, 3929, 4062, 4132, 4145, 4163, 4189, 4204, 4228, 4246, 4266, 4311, 4342, 4359, 4374], 'Scopus': [414, 456, 537, 639, 662, 754, 773, 812, 827, 875, 888, 949, 993, 1053, 1091, 1106, 1226, 1279, 1337, 1392, 1464, 2014, 2079, 3873, 3886, 3930, 4063, 4133, 4146, 4164, 4205, 4229, 4247, 4267, 4312, 4343, 4360, 4375], '(1619)': [415], 'Google': [416, 458, 493, 520, 539, 613, 641, 664, 756, 775, 795, 814, 829, 877, 890, 929, 951, 971, 995, 1015, 1033, 1055, 1093, 1108, 1228, 1281, 1339, 1394, 1434, 1466, 2016, 2081, 3875, 3888, 3932, 4065, 4135, 4148, 4166, 4190, 4207, 4231, 4249, 4269, 4314, 4345, 4362, 4377], 'Scholar).': [417, 459, 540, 689, 830, 891, 1056, 1109, 1229, 1282, 1340, 1395, 1435, 1467, 4066, 4270, 4378], 'anabolic': [419], 'mitogenic': [421, 1073, 3706], 'actions': [422], 'mediated': [426], 'largely': [427], 'through': [428], '1': [431, 1799, 2048, 2286, 2296, 2301, 2330, 2376, 2517, 2805], 'receptor,': [433, 438, 3590], 'which,': [434], 'like': [435], 'heterotetrameric,': [441], 'membrane-spanning': [442], 'tyrosine': [443, 4289], 'kinase': [444, 4290], '(2Yardin': [445], 'Y.': [446, 502, 616, 620, 671, 919, 954, 974, 998, 1314, 1318, 1380, 2003, 3812, 3816, 3907, 3911, 3939, 4052], 'Ullrich': [447], 'A.': [448, 657, 685, 807, 1020, 3953, 4169], 'Annu.': [449], 'Biochem.': [451, 2074], '1988;': [452, 4308], '57:': [453], '443-478Crossref': [454], '(1391)': [457], 'It': [460, 2860, 4379], 'has': [461, 3661, 3763], 'accepted': [463], 'dogma': [464, 3609], 'that,': [465], 'unlike': [466], 'bind': [470, 1148, 1163, 2538, 2609, 3221, 3580, 3627, 3743, 3757, 3794, 3961], 'specificity': [482, 2574], '(3Jones': [483], 'J.I.': [484], 'Clemmons': [485, 766], 'D.R.': [486, 767, 1215], '1995;': [489, 658, 984, 1029, 4186], '16:': [490], '3-34Crossref': [491], 'Scholar,': [494, 521, 614, 642, 665, 757, 776, 796, 815, 878, 930, 952, 972, 996, 1016, 1034, 1094, 3876, 3933, 4136, 4149, 4167, 4191, 4208, 4232, 4250, 4315, 4346, 4363], '4Rosenfeld': [495], 'R.G.': [496, 626, 678, 866, 923, 960, 980, 1004, 1084, 1324, 1386, 2005, 3864, 3917, 3946, 4054, 4124, 4155, 4199], 'Lamson': [497, 863, 957, 1079, 3861, 4121], 'G.': [498, 864, 958, 1080, 3814, 3820, 3862, 4122, 4195], 'Pham': [499, 861, 1001, 3859, 4119], 'H.': [500, 862, 932, 1002, 1382, 3860, 4120, 4352, 4365], 'Oh': [501, 670, 918, 1379, 2002, 3938, 4051], 'Conover': [503], 'C.': [504, 880, 1096, 1098, 1270, 1560, 3878, 4138, 4214, 4254, 4256, 4459], 'De': [505], 'L.D.': [506], 'Donovan': [507], 'S.M.': [508], 'Ocrant': [509], 'I.': [510], 'Giudice': [511], 'L.': [512, 978], 'Recent': [513, 892], 'Prog.': [514, 526], 'Horm.': [515], 'Res.': [516, 529, 925], '1990;': [517, 871, 1222, 1275, 3869, 4129, 4201, 4225], '46:': [518], '99-159PubMed': [519], '5Shimasaki': [522], 'S.': [523, 656, 684, 778, 806, 2070, 3952], 'Ling': [524, 783, 1383], 'N.': [525, 784, 1384], 'Growth': [527, 608, 1273], 'Factor': [528], '1991;': [530, 750, 769, 788, 1388], '3:': [531, 1276], '243-266Abstract': [532], 'Full': [533, 633, 635, 791, 943, 945, 967, 987, 989, 1011, 1047, 1049, 1331, 1333, 1430, 3924, 3926], 'Text': [534, 634, 636, 792, 944, 946, 968, 988, 990, 1012, 1048, 1050, 1332, 1334, 1431, 3925, 3927], 'PDF': [535, 637, 793, 947, 969, 991, 1013, 1051, 1335, 1432, 3928], '(649)': [538], 'characterized': [544, 575, 4276], 'significant': [547], 'sequence': [548, 706, 1841, 2795, 2982], 'homology,': [549], 'including': [550, 701, 4101], 'GCGCCXXC': [552], 'motif': [553], 'part': [555], '10–12': [557], 'cysteines': [559, 567, 2797, 2809, 2819], 'at': [560, 568, 1587, 1606, 1660, 1675, 1908, 1916, 2031, 2050, 2092, 2169, 2178, 2210, 2216, 2223, 2268, 2332, 2353, 2378, 2798, 2824, 2946, 2983, 3042, 3251, 3316, 3495, 3511, 3649], 'terminus': [563, 2801], 'carboxyl': [570], 'recently': [574, 3636], 'two': [576, 589], 'additional': [577, 590, 3891], 'secreted': [578], 'lower': [581, 705, 3447, 3652], '(IGFBP-7/mac25': [585], 'IGFBP-8/CTGF)': [587], 'potential': [591, 4443], 'members': [592], '(6Murphy': [597], 'M.': [598, 780, 882, 936, 1100, 2072, 3880, 4140, 4216, 4218, 4220, 4329], 'Pykett': [599], 'M.J.': [600], 'Harnish': [601], 'Zang': [603], 'K.D.': [604], 'George': [605], 'D.L.': [606], 'Cell': [607], 'Differ.': [609], '1993;': [610, 964, 1008, 1087, 4263], '4:': [611], '715-722PubMed': [612], '7Oh': [615], 'Nagalla': [617, 668, 1315, 3908, 3936], 'S.R.': [618, 669, 1316, 3909, 3937], 'Yamanaka': [619, 1259, 1317, 3910], 'Kim': [621, 1319, 3912], 'H.-S.': [622, 667, 1320, 3913, 3935], 'Wilson': [623, 672, 1321, 1997, 3914, 3940, 4180], 'E.': [624, 673, 1322, 3915, 3941], 'Rosenfeld': [625, 677, 744, 865, 922, 959, 979, 1003, 1083, 1323, 1385, 2004, 3863, 3916, 3945, 4053, 4123, 4154, 4198], 'J.': [627, 746, 785, 867, 937, 961, 981, 1005, 1041, 1218, 1264, 1268, 1325, 1424, 1456, 1479, 2006, 3865, 3918, 4055, 4125, 4156, 4177, 4182, 4221, 4239, 4252, 4260, 4305, 4336, 4465], 'Biol.': [628, 786, 938, 962, 982, 1006, 1042, 1326, 1425, 3919], 'Chem.': [629, 787, 939, 963, 983, 1007, 1043, 1327, 1426, 3920], '1996;': [630, 823, 926, 940, 1102, 1328, 3921], '271:': [631, 941, 1329, 3922], '30322-30325Abstract': [632, 1330, 3923], '(311)': [640, 1338, 3931], '8Swisshelm': [643], 'K.': [644, 646, 648, 4153], 'Ryan': [645], 'Tsuchiya': [647], 'Sager': [649], 'R.': [650, 745, 1024, 1036, 1204, 3819], 'Proc.': [651, 679, 801, 3947], 'Natl.': [652, 680, 802, 3948], 'Acad.': [653, 681, 803, 3949], 'Sci.': [654, 682, 804, 3950], 'U.': [655, 683, 805, 3951], '92:': [659], '4472-4476Crossref': [660], '(198)': [663], '9Kim': [666, 3934], 'Roberts': [674, 3942], 'Jr.,': [675, 3943, 4462], 'C.T.': [676, 3944], '1997;': [686, 1044, 2010, 3954, 4059], '(in': [687, 3955], 'press)Google': [688, 3956], 'structure': [691, 2899, 2941, 3067, 3094, 3211, 3229], 'revealed': [694, 2624, 3779], 'presence': [696, 1783, 1808, 2754, 3306, 4023], 'amino-terminal': [698], 'sequences,': [700], '11': [702, 2815], 'cysteines,': [703], 'normally': [710, 2647], 'well-conserved': [711], '1–6': [715, 2536, 2567, 2645, 3241, 3629], 'function': [719], 'carrier': [721], 'IGFs,': [724, 3966], 'delaying': [725], 'degradation': [726], 'peptides': [729, 4420], 'increasing': [731], 'half-lives': [733], 'access': [737, 851], 'receptors': [739, 856, 3337, 3361, 4411], '(10Cohen': [740], 'Peehl': [742], 'D.M.': [743], 'Clin.': [747, 868, 1219, 1457, 2007, 3866, 4056, 4126, 4157, 4183, 4222, 4240, 4306, 4337], 'Endocrinol.': [748, 869, 1028, 1086, 1220, 1458, 2008, 3867, 4057, 4127, 4158, 4184, 4223, 4241], 'Metab.': [749, 870, 1221, 1459, 2009, 3868, 4058, 4128, 4159, 4185, 4224, 4242, 4369], '73:': [751], '401-407Crossref': [752], '(344)': [755], '11McCusker': [758], 'R.H.': [759], 'Busby': [760], 'W.H.': [761], 'Dehoff': [762], 'M.H.': [763], 'Camacho': [764], 'H.C.': [765], 'Endocrinology.': [768, 822, 883, 1101, 1387, 3881, 4141, 4200], '129:': [770], '939-949Crossref': [771], '(97)': [774], '12Shimasaki': [777], 'Shimonaka': [779], 'Zhang': [781, 1381], 'H.P.': [782], '266:': [789], '10646-10653Abstract': [790], '13Baxter': [797], 'R.C.': [798, 4236], 'Martin': [799], 'J.L.': [800], '86:': [809], '6898-6902Crossref': [810], '(304)': [813], '14Conover': [816], 'C.A.': [817], 'Clarkson': [818], 'J.T.': [819], 'Bale': [820], 'L.K.': [821], '137:': [824, 1103], '2286-2292Crossref': [825], '(49)': [828], 'Proteolysis': [831], 'IGFBPs,': [833, 900, 4082], 'observed': [835], 'during': [836, 2902], 'results': [838, 3052, 3846], 'fragments': [841, 1063, 1127, 1146, 3714, 3806, 3849, 4075, 4394], 'decreased': [843, 3851, 4286], 'and,': [847], 'thereby,': [848], 'promotes': [849], '(15Giudice': [857, 3855, 4115], 'L.C.': [858, 3856, 4116], 'Farrell': [859, 3857, 4117], 'E.M.': [860, 1272, 2001, 3858, 4050, 4118], '71:': [872, 3870, 4130, 4226], '806-816Crossref': [873, 3871, 4131], '(375)': [876, 3874, 4134], '16Lassarre': [879, 3877, 4137], 'Binoux': [881, 1099, 2071, 3879, 4139, 4219], '1994;': [884, 3882, 4142, 4160], '134:': [885, 3883, 4143], '1254-1262Crossref': [886, 3884, 4144], '(105)': [889, 3887, 4147], 'studies': [893, 2719, 3381, 3777, 3827, 4014, 4068], 'demonstrated': [895, 1152, 2855, 2906, 3563, 3829, 4021], 'several': [897, 3665], 'these': [899, 1111, 2605, 3512, 4273], 'especially': [901, 2873], 'IGFBP-3,': [902, 2088, 2174, 2261, 3312, 3315, 3392, 3703, 4077], 'may': [903, 2694, 3667, 3715, 4407], 'capable': [906, 1069, 2743], 'directly': [908], 'cell': [910, 1129, 4036], 'IGF-independent': [914], 'manner': [915, 2484], '(17Gucev': [916], 'Z.S.': [917], 'Kelley': [920], 'K.M.': [921], 'Cancer': [924], '56:': [927], '1545-1550PubMed': [928], '18Huynh': [931], 'Yang': [933], 'X.': [934], 'Pollak': [935], '1016-1021Abstract': [942], '(206)': [950], '19Oh': [953], 'Muller': [955, 975, 999], 'H.L.': [956, 976, 1000], '268:': [965, 1009], '14964-14971Abstract': [966], '20Oh': [973], 'Ng': [977], '270:': [985], '13589-13592Abstract': [986], '(225)': [994], '21Oh': [997], '26045-26048Abstract': [1010], '22Valentinis': [1017], 'B.': [1018, 1038, 1478, 2068, 4212, 4367, 4464], 'Bhala': [1019], 'DeAngelis': [1021], 'T.': [1022, 1082, 1561, 4350, 4460, 4471], 'Baserga': [1023], 'Cohen': [1025, 1039], 'Mol.': [1027, 1085], '9:': [1030], '361-367Crossref': [1031], '23Rajah': [1035], 'Valentinis': [1037], '272:': [1045], '12181-12188Abstract': [1046], '(674)': [1054], 'Both': [1057], 'intact': [1058, 3012, 3702], 'proteolytic': [1062, 1145], 'shown': [1066, 2488, 3638, 3663], 'blocking': [1071], 'effect': [1074, 1122, 3457, 3707], '(24Cohen': [1077], 'Okajima': [1081], '7:': [1088], '380-386Crossref': [1089], '(128)': [1092], '25Lalou': [1095], 'Lassarre': [1097, 4213], '3206-3212Crossref': [1104], '(148)': [1107], 'Whether': [1110], 'effects': [1112], 'reflect': [1113, 3554, 4389], 'inhibition': [1114, 3494, 3594, 3771], 'signaling': [1117, 3463, 3722, 4296], 'pathways': [1118, 4439], 'direct': [1121], 'its': [1126, 1172, 4001], 'on': [1128, 2508, 2727, 3460, 3807], 'remains': [1131], 'unclear.': [1132], 'have,': [1134], 'therefore,': [1135], 'reevaluated': [1136], 'ability': [1138, 3578, 3625, 3718, 3739, 3755], '1–6,': [1141, 2784], '(IGFBP-3(1–87))': [1160], 'not': [1161, 3324, 3383, 3391, 3553, 3701], 'only': [1162, 3621], 'subsequently': [1175, 3583, 4090], 'insulin-stimulated': [1177, 3478, 3530, 3596], 'IRS-1.': [1188, 3607], 'High': [1189, 1593, 1903], 'performance': [1190], 'liquid': [1191], 'chromatography-purified': [1192], 'hIGFBP-1': [1193], 'human': [1195, 1231, 1284, 1552, 2243, 2970, 3300, 3334, 3792], 'amniotic': [1196, 4045], 'fluid': [1197], 'was': [1198, 1245, 1303, 1342, 1350, 1357, 1372, 1472, 1492, 1509, 1515, 1613, 1689, 1768, 1790, 1817, 1834, 1861, 1897, 1921, 1926, 1947, 1992, 2055, 2273, 2463, 2560, 2616, 2680, 2704, 2977, 2994, 3003, 3124, 3338, 3375, 3472, 3509, 3534], 'kindly': [1199, 1351, 1502, 1556], 'provided': [1200, 1352, 1503], 'Dr.': [1202, 1477, 1559], 'D.': [1203, 1266, 2066, 4300, 4323], 'Powell': [1205, 1214], '(Baylor': [1206], 'College': [1207], 'Medicine,': [1209], 'Houston,': [1210], 'TX)': [1211], '(26Liu': [1212], 'F.': [1213, 4197, 4234, 4327], 'Hintz': [1216, 4237], 'R.L.': [1217, 4238], '70:': [1223], '620-628Crossref': [1224], '(59)': [1227], 'Recombinant': [1230, 1283, 1895], '(rhIGFBP-3),': [1233], 'nonglycosylated': [1235], '29': [1236], 'kDa': [1237, 2503], 'core': [1238], 'protein': [1239, 1896, 1925, 1946, 3414, 3979, 4027], 'expressed': [1240, 2444, 2969], 'Escherichia': [1242], 'coli': [1243], 'cells,': [1244, 1877], 'generous': [1247, 1474], 'gift': [1248, 1475], 'Celtrix,': [1250], 'Inc.': [1251, 1617, 1631], '(Santa': [1252], 'Clara,': [1253], 'CA)': [1254], '(27Spratt': [1255], 'S.K.': [1256], 'Tatsuno': [1257], 'G.P.': [1258], 'M.K.': [1260, 4335], 'Ark': [1261], 'B.C.': [1262], 'Detmer': [1263], 'Mascarenhas': [1265], 'Flynn': [1267], 'Talkington-Verser': [1269], 'Spencer': [1271], 'Factors.': [1274], '63-72Crossref': [1277], '(31)': [1280], 'IGFBP-2,': [1285], '-4,': [1286], '-5,': [1287], '-6': [1289], 'were': [1290, 1308, 1398, 1440, 1501, 1541, 1555, 1596, 1626, 1643, 1705, 1713, 1881, 1968, 2122, 2131, 2137, 2164, 2214, 2228, 2231, 2247, 2305, 2320, 2358, 2383, 2393, 2404, 2417, 2425, 2506, 3139, 3152, 3294, 4083], 'purchased': [1291, 1343, 1358, 1493, 1542, 1627], 'Austral': [1293], 'Biologicals': [1294], '(San': [1295], 'Ramon,': [1296], 'CA).': [1297, 1348, 1547, 1619, 2441], 'cDNA': [1299, 2246], '(mac25)': [1302], 'cloned,': [1304], 'baculovirus': [1306, 1611, 1865, 2974], 'recombinants': [1307, 1880], 'made': [1309], 'described': [1311, 1375, 1995, 2058], '(7Oh': [1313, 3906], 'IGF-I': [1341, 1531, 1786, 3644], 'Bachem': [1345], 'California': [1346], '(Torrance,': [1347], 'IGF-II': [1349, 1366, 1370, 2637, 2639, 2666, 3646], 'Lilly.': [1354], 'Bovine': [1355], 'Sigma.': [1360], '[(Gln6,': [1361], 'Ala7,': [1362], 'Thr18,': [1363], 'Leu19,': [1364], 'Leu27]': [1365], '([QAYLL]IGF-II),': [1367], 'synthetic': [1369], 'analog,': [1371], 'synthesized': [1373], 'previously': [1376], '(28Beukers': [1377], 'M.W.': [1378], '128:': [1389], '1201-1203Crossref': [1390], '(73)': [1393], 'Human': [1396], 'placentas': [1397], 'stripped': [1399], 'membranes,': [1402], 'washed': [1403], '0.25': [1405], 'm': [1406], 'sucrose,': [1407], 'homogenized': [1409], 'polytron': [1412], '(29Casella': [1413], 'S.J.': [1414, 1450], 'Han': [1415], 'V.K.': [1416], "D'Ercole": [1417], 'A.J.': [1418], 'Svoboda': [1419], 'M.E.': [1420], 'Van': [1421, 1453], 'Wyk': [1422, 1454], 'J.J.': [1423, 1455], '1986;': [1427, 2075, 4339], '261:': [1428], '9268-9273Abstract': [1429], 'Crude': [1436], 'microsomal': [1437, 2191, 3302], 'membrane': [1438], 'preparations': [1439], 'obtained': [1441, 1510, 1614], 'via': [1442], 'differential': [1443], 'centrifugation': [1444], '(30Marshall': [1445], 'R.N.': [1446], 'Underwood': [1447], 'L.E.': [1448], 'Voina': [1449], 'Foushee': [1451], 'D.B.': [1452], '1974;': [1460], '39:': [1461], '283-292Crossref': [1462], '(239)': [1465], 'Anti-phosphotyrosine': [1468], 'monoclonal': [1469, 2340], 'antibody': [1470, 1889, 2025, 2341, 2397, 2410], '(4G10)': [1471], 'Druker': [1480, 4466], '(Dept.': [1481, 1564], 'Hematology': [1483], 'Medical': [1485], 'Oncology,': [1486], 'Oregon': [1487, 1567], 'Health': [1488, 1568], 'Sciences': [1489, 1569], 'University).125I-(A14)-monoiodinated': [1490], 'Amersham': [1495, 1512], 'Corp.': [1496, 1513], '125I-labeled': [1497, 1734], 'hormone': [1499, 1736, 2593], 'and125I-prolactin': [1500], 'DSL': [1505], '(Webster,': [1506], 'TX).': [1507], 'Na125I': [1508], 'Iodination': [1514], 'performed': [1516, 1818, 1993, 2056, 2464, 3295], 'modification': [1519, 3976], 'chloramine-T': [1522], 'technique': [1523, 1991], 'specific': [1525, 3329, 4017], 'activities': [1526], '350–500': [1528], 'μCi/μg': [1529], '-II.': [1533], 'Reagents': [1534], 'SDS-polyacrylamide': [1537], 'electrophoresis': [1539], '(PAGE)': [1540], 'Bio-Rad': [1544], 'Laboratories': [1545], '(Richmond,': [1546], 'NIH-3T3': [1548, 2237], 'cells': [1549, 1595, 1905, 2238], 'overexpressing': [1550], 'gifted': [1557], 'Roberts,': [1562, 4461], 'Jr.': [1563], 'Pediatrics,': [1566], 'University)': [1570], 'grown': [1572], "Dulbecco's": [1574], 'modified': [1575, 3088, 3838], "Eagle's": [1576], 'medium': [1577], '+': [1578, 1583, 2348], '10%': [1579, 2291], 'fetal': [1580], 'calf': [1581], 'serum': [1582, 4048, 4088], '500': [1584, 2196], 'μg/ml': [1585], 'geneticin': [1586], '37': [1588], '°C': [1589, 2033, 2171], '5%': [1591, 2325], 'CO2.': [1592], 'Five': [1594, 1904], 'maintained': [1597], 'ExCell': [1599], '405': [1600], 'Media': [1601], '(JRH': [1602], 'Biosciences,': [1603], 'Lenexa,': [1604], 'KS)': [1605], '27': [1607, 1917], '°C.': [1608, 1677, 1918, 2212, 2225, 2270, 2355], 'wild-type': [1610], '(AcNPv)': [1612], 'Invitrogen': [1616], '(Carlsbad,': [1618], 'All': [1620], 'tissue': [1621], 'culture': [1622], 'media': [1623, 1901, 1920, 4031], 'components': [1625], 'Life': [1629], 'Technologies,': [1630, 1870], 'Aliquots': [1632], 'reagents': [1634], 'plus': [1635], 'buffer': [1637, 2104, 2200, 2277], '(50': [1638, 2201], 'mm': [1639, 2106, 2119, 2282, 2289, 2297], 'Tris-HCl,': [1640, 2107, 2283], 'pH': [1641, 2108, 2205, 2284], '7.4)': [1642, 2206], 'incubated': [1644, 2138, 2186, 2337, 2362, 3153], 'with125I-insulin': [1645, 2600, 3154], '(20,000': [1646, 1649, 1653], 'cpm),': [1647, 1650], '125I-IGF-I': [1648, 2150, 2466, 2504], '125I-IGF-II': [1652], 'cpm)': [1654], 'without': [1657, 2117, 3145], 'indicated': [1658, 1663, 2095, 2180], 'reagents,': [1659], 'concentrations': [1662, 2094, 2179, 3317, 3496, 3556, 4391], 'under': [1664, 3994], '"Results"': [1665], 'Figs.': [1668], '1,': [1669], '2,': [1670], '3': [1671, 1912, 1914, 2250], '16': [1673, 2029, 2208], 'h': [1674, 2030, 2049, 2168, 2209, 2267, 2331, 2377], '4': [1676, 2032, 2170, 2211, 2224, 2269, 2354], 'At': [1678], 'end': [1680, 2986], 'incubation,': [1682], 'cross-linking': [1684, 1699, 1761, 2462, 2471, 2623, 2890, 3380, 3431], 'reagent': [1685], 'disuccinimidyl': [1686], 'suberate': [1687], '(Pierce)': [1688], 'added': [1690], 'final': [1693], 'concentration': [1694], '0.5': [1696], 'mm.': [1697], 'After': [1698, 1857, 2226], '15': [1701], 'min,': [1702], 'samples': [1704, 2227, 3560], 'subjected': [1706, 1948, 2405, 2418, 3125, 3140], '12%': [1708], 'SDS-PAGE': [1709, 1950, 2125, 2308, 2510, 3127, 3142], 'autoradiography.': [1711], 'Bands': [1712], 'quantified': [1714], 'densitometry,': [1716], 'calculated': [1718], 'densitometer': [1721], '(Bio-Rad).Figure': [1722], '2Specificity': [1723], 'to125I-insulin.': [1727], 'Autoradiogram': [1728], 'of125I-insulin': [1729, 2145, 2163], '(A),': [1730], '125I-prolactin': [1731, 2589], '(B),': [1732], '(C)': [1737], 'cross-linked': [1738, 1769, 1791], '20': [1740, 1771, 1793, 2281], 'pmol': [1741, 1772, 1794, 1800, 3387, 3499, 3541], 'IGFBP-1,': [1743, 2087, 2584], '-3,': [1744, 2585, 2912], '-7,': [1746], 'Fig.': [1749, 1821, 2516, 3420], '1.View': [1750, 1822], 'Large': [1751, 1823, 3159, 3271], 'Image': [1752, 1824, 3160, 3272], 'Figure': [1753, 1825, 3161, 3273], 'ViewerDownload': [1754, 1826, 3162, 3274], 'Hi-res': [1755, 1827, 3163, 3275], 'image': [1756, 1828, 3164, 3276], 'Download': [1757, 1829, 3165, 3277], '(PPT)Figure': [1758, 3166], '3Competitive': [1759], '-3.': [1765], 'A,': [1766, 3119], '125I-insulin': [1767, 2475, 2615, 2679, 3297, 3332], '(top)': [1775, 1797], '(bottom)': [1778, 1803], 'alone': [1779, 1804], 'unlabeled': [1785, 1810, 2173, 3310], 'B,125I-IGF-II': [1789], 'IGF-II,': [1811, 1813], '[QAYLL]': [1812, 2636, 2665], 'Cross-linking': [1816], '(PPT)': [1830, 3278], 'Polymerase': [1831], 'chain': [1832], 'reaction': [1833, 2272], 'add': [1837], 'FLAG': [1839, 1942, 2981], 'epitope': [1840], '(DYKDDDDK)': [1842], 'new': [1845, 4444], 'stop': [1846], 'codon': [1847], 'immediately': [1848], 'following': [1849, 3841], '87': [1852], 'mature': [1855, 4026], 'IGFBP-3.': [1856], 'sequencing,': [1858], 'this': [1859, 2966, 4385], 'subcloned': [1862], 'into': [1863, 1874], 'expression': [1866], 'vector': [1867], 'pFASTBAC1': [1868], '(Life': [1869], 'Inc.)': [1871], 'transfected': [1873, 2240], 'Sf9': [1875], 'insect': [1876], 'viral': [1879], 'immunoblotting': [1884], 'anti-FLAG': [1887, 1929, 2023], 'M2': [1888, 1930, 2024], '(Eastman': [1890], 'Kodak,': [1891], 'New': [1892], 'Haven,': [1893], 'CT).': [1894], 'purified': [1898, 1927, 1945, 3121], 'after': [1906], 'infecting': [1907], 'm.o.i.': [1910], '=': [1911, 2715], 'days': [1915], 'collected,': [1922], 'over': [1928], 'beads': [1932], 'according': [1933], 'manufacturer': [1936], 'protocol': [1937], 'elution': [1939], 'peptide.': [1943], '15%': [1953], 'stained': [1956], 'Coomassie': [1958], 'Blue': [1959], 'transferred': [1961], 'nitrocellulose': [1963, 2134], 'immunodetection.': [1965], 'Protein': [1966], 'fractions': [1967], 'pooled,': [1969], 'concentrated,': [1970], 'quantitated': [1972], 'comparison': [1974], 'known': [1976], 'amounts': [1977], 'BSA': [1979], 'silver': [1981], 'staining': [1982], '(Bio-Rad).': [1983], 'Immunoblotting': [1984], 'using': [1985, 2018, 2385, 2408, 2421, 2432, 3296], 'chemiluminescence': [1988], '(ECL)': [1989], 'detection': [1990, 2388], 'et': [1998, 2061], 'al.': [1999, 2062], '(31Wilson': [2000, 4049], '82:': [2011, 4060, 4309], '1301-1303Crossref': [2012, 4061], '(51)': [2015, 4064], 'Scholar)': [2017, 2082], '1:3000': [2020, 2038, 2365], 'dilution': [2021, 2039, 2366], 'incubating': [2027], 'then': [2035, 2185, 2336, 2359, 3130], 'anti-mouse': [2041, 2369], 'IgG': [2042], 'horseradish': [2043, 2371], 'peroxidase': [2044, 2372], '(Amersham': [2045, 2373], 'Corp.)': [2046, 2374], 'room': [2051, 2333, 2379], 'temperature.': [2052, 2380], 'Ligand': [2053], 'blotting': [2054], 'Hossenlopp': [2060], '(32Hossenlopp': [2063], 'Seurin': [2065], 'Segovia-Quinson': [2067], 'Hardouin': [2069], 'Anal.': [2073], '154:': [2076], '138-143Crossref': [2077], '(1199)': [2080], 'minor': [2084], 'modifications.': [2085], 'Briefly,': [2086], 'IGFBP-3(1–87),': [2089, 2262, 2998, 3007], 'text': [2098], 'figures': [2100], 'SDS': [2102], 'sample': [2103], '(62.5': [2105], '6.8,': [2109], '40%': [2110], 'glycerol,': [2111, 2292], '2.3%': [2113], 'SDS)': [2114], '100': [2118, 2253, 3345, 3498, 3540], 'dithiothreitol': [2120], '(DTT)': [2121], 'analyzed': [2123, 2426], '(12': [2126], '15%).': [2128], 'Separated': [2129], 'electroblotted': [2132, 3148], 'onto': [2133, 3149], 'filters,': [2135, 3150], 'which': [2136, 2256, 2976, 3151], 'overnight': [2139, 2352], '1.5': [2141], '×': [2142, 2218], '106': [2143], 'cpm': [2144, 2162], 'mixture': [2148], 'and125I-IGF-II,': [2151], 'washed,': [2152], 'dried,': [2153], 'exposed': [2155, 2248], 'film': [2157], '(Biomax;': [2158], 'Eastman': [2159], 'Kodak).': [2160], '20,000': [2161], 'preincubated': [2165, 2259], '2': [2167, 2266, 2595, 2602], 'figure': [2183], '50': [2188], 'μg': [2189], 'placental': [2192, 3301, 3335, 3371, 3397, 3526], 'crude': [2193, 3299], 'membranes': [2194, 3303, 3372], 'μl': [2197], 'mmTris-HCl,': [2202], '0.5%': [2203], 'BSA,': [2204], 'Samples': [2213], 'centrifuged': [2215], '10,000': [2217], 'g': [2219], '10': [2221], 'min': [2222, 2251], 'centrifuged,': [2229], 'pellets': [2230], 'counted': [2232], 'γ-counter.': [2235], 'Confluent': [2236], 'stably': [2239], 'ng/ml': [2254], 'had': [2257], 'quenched': [2274], 'solubilization': [2276], '(1%': [2278], 'Nonidet': [2279], 'P-40,': [2280], '8.0,': [2285], 'mmEDTA,': [2287], '150': [2288], 'NaCl,': [2290], '12': [2293, 2818], 'units/ml': [2294], 'aprotinin,': [2295], 'phenylmethylsulfonyl': [2298], 'fluoride,': [2299], 'mmNa3VO4).': [2302], 'Solubilized': [2303], 'separated': [2306], '(8%)': [2309], 'visualized': [2311, 2384], 'immunoblot': [2313, 2316, 2407, 2420, 3132], 'analysis.': [2314, 2570], 'For': [2315], 'analysis,': [2317], 'filters': [2319, 2357], 'blocked': [2321], 'TBS-T': [2323], 'containing': [2324], 'non-fat': [2326], 'dry': [2327], 'milk': [2328], 'temperature': [2334], 'anti-phosphotyrosine': [2339, 2409], '(1.5': [2342], 'μg/ml)': [2343], 'diluted': [2344], 'Tris-buffered': [2346], 'saline': [2347], '0.1%': [2349], 'Triton': [2350], 'X-100': [2351], 'rinsed': [2360], 'goat': [2368], 'IgG-conjugated': [2370], 'Immunoreactive': [2381], 'ECL': [2387], 'system.': [2389], 'Alternatively,': [2390], 'solubilized': [2391, 2415], 'immunoprecipitated': [2394], 'anti-IRS-1': [2396, 2422], '(Upstate': [2398], 'Biotechnology,': [2399], 'Lake': [2400], 'Placid,': [2401], 'NY)': [2402], 'above.': [2412], 'In': [2413, 2512, 2551, 2655, 3633, 3731], 'parallel,': [2414], 'antibody.': [2423, 3135], 'Data': [2424], 'two-tailed': [2429], "Student's": [2430], 't-test,': [2431], 'software': [2434], 'program': [2435], 'Instat': [2436], '2.01': [2437], '(Graphpad,': [2438], 'San': [2439], 'Diego,': [2440], 'Values': [2442], 'means': [2446], '±': [2447], 'S.D.': [2448], 'To': [2449, 2571, 2963, 3077], 'evaluate': [2450], '1–7': [2455, 2525], '+125I-IGF-II': [2467], '125I-insulin.': [2469], 'Affinity': [2470], 'shows': [2476], 'dose-dependent': [2483, 3488], '(Fig.1': [2485], 'A).': [2486, 2603, 2988, 3507], 'As': [2487], 'Fig.1': [2490], 'B,': [2491, 2518], 'top': [2492], 'panel,': [2493, 2520], 'expected': [2495], 'sizes': [2496], 'individual': [2498], 'coupled': [2500], '7': [2502], 'or125I-IGF-II': [2505], 'detected': [2507], 'gel.': [2511], 'similar': [2514, 2708], 'way,': [2515], 'bottom': [2519], 'showed125I-insulin': [2521], 'bound': [2522], 'proper': [2527, 2838], 'size': [2528], 'bands.': [2530], 'This': [2531, 2892, 3399], 'data': [2532, 2762, 2933, 3570], 'demonstrates': [2533], 'significantly': [2542, 3004, 3726], 'reduced': [2543, 3244, 3555, 3727], 'compared': [2545, 2779, 2879, 3008], 'affinities': [2548, 2628, 2657, 3429], 'IGFs.': [2550, 3076, 3175, 3730], 'contrast,': [2552, 2656], 'ratio': [2554], 'insulin:IGF': [2556], '500-fold': [2562], 'higher': [2563, 3409], 'than': [2564, 2650, 3442, 3449, 3654], 'densitometric': [2569], 'establish': [2572], 'we': [2580, 2968, 3635, 3735], 'attempted': [2581], 'cross-link': [2583], '-7': [2587, 2676, 2914], '(Fig.2': [2590], 'B)': [2591], 'and125I-growth': [2592], '(Fig.': [2594, 2601, 2667, 3014, 3352, 3505, 3547], 'C),': [2596], 'Although': [2604, 3422], 'failed': [2607], 'proteins,': [2612], 'confirmed.': [2617], 'Furthermore,': [2618], 'analysis': [2619], 'competitive': [2621], 'relative': [2627], '≥': [2633, 2635], '(an': [2638], 'analog': [2640], 'whose': [2641], '100-fold': [2648], 'less': [2649, 2869], 'native': [2653], 'IGF-II).': [2654], '≫': [2662], '>': [2664], '3,A': [2668], 'B).': [2670, 3549], 'to125I-IGFs': [2677], 'competitively': [2681], 'displaced': [2682], 'both': [2684, 2728, 2756, 2842, 3643], 'suggesting': [2688, 3032, 3686, 3710], 'site': [2693, 2740, 3250], 'at,': [2696], 'near,': [2698], 'site.': [2702], 'found': [2705, 2820, 4093], '(IC50': [2714], '20–34': [2716], 'nm).': [2717], 'Previous': [2718], 'suggested': [2721, 3418], 'sites': [2725], 'reside': [2726], 'NH2-': [2730, 2843], 'COOH-terminal': [2732, 2845, 3104, 3181], 'molecule;': [2737], 'each': [2738], 'individually': [2742], 'low-affinity': [2745], 'binding,': [2746, 2885, 4414], 'whereas': [2747], 'requires': [2752], 'domains.': [2758, 2847], 'Taken': [2759, 3567], 'together,': [2760, 3568], 'our': [2761, 3569, 4447], 'suggest': [2763, 3053, 4441], 'relatively': [2774, 2953, 3797], 'those': [2781], 'attributed': [2787], 'lack': [2790], '(only': [2804], '6': [2808], 'conserved)': [2811], 'although': [2812, 3445], 'retains': [2814], 'NH2': [2826, 3059], 'High-affinity': [2828], 'thus': [2834, 4426], 'appears': [2835, 2861, 3434], 'require': [2837], 'structural': [2839], 'configuration': [2840], 'involving': [2841], 'ligand-binding': [2846], 'Insulin': [2848, 3290], 'further': [2854, 2964, 3232, 3376, 3776], 'use': [2857], 'WLB.': [2859], 'much': [2868, 4415], 'effective': [2870], 'WLBs,': [2872], 'absence': [2876, 3308], 'DTT': [2878, 2916, 3022], 'seen': [2882], 'solution': [2884], 'assessed': [2887], '(Fig.1).': [2891], 'presumably': [2893, 3406], 'reflects': [2894, 3407], 'changes': [2895], 'tertiary': [2898, 2940], 'SDS-PAGE.': [2903], 'However,': [2904, 3659], 'WLB': [2905], 'reduction': [2908, 3223, 3981], '-1,': [2911], 'resulted': [2917, 3023], 'marked': [2920], 'decrease': [2921], 'increased': [2927, 3005, 3262, 3764, 3974, 4390], '(Fig.4).': [2931], 'These': [2932, 3051, 3550, 4405, 4424], 'indicate': [2934, 3899], 'molecules': [2944], 'are,': [2945], 'least': [2947, 3043, 3650], 'part,': [2949, 3045], 'responsible': [2950], 'IGF.': [2962], 'test': [2965], 'hypothesis,': [2967], 'IGFBP-3(1–87)': [2971, 3020, 3038, 3123, 3138, 3474, 3501, 3543, 3575], 'system,': [2975], 'epitope-tagged': [2978], '(Fig.5': [2987], 'While': [2989], 'greatly': [2995], 'diminished': [2996, 3267], '5,': [3015], 'B': [3016], 'andC).': [3017], 'Reduction': [3018], 'modest': [3026], 'increase': [3027], 'within': [3036], 'still': [3040, 3220], 'limit,': [3041], 'between': [3057, 3401, 3615], 'termini': [3062], 'result': [3063, 3192], 'ternary': [3066, 3093, 3186, 3210], 'confers': [3072], 'enhance': [3078], 'molecule': [3085, 3257], 'must': [3086, 3424, 3836], 'either': [3090, 3243, 3783], 'disrupting': [3091], '(under': [3095], 'reducing': [3096], 'conditions)': [3097], 'eliminating': [3100], 'modifying': [3102], 'domain': [3105], '(IGFBP-3(1–87)': [3106], 'IGFBP-7).': [3108], 'A': [3109], 'schematic': [3110], 'model': [3111, 4430], 'depicted': [3113], 'Fig.6.Figure': [3115], '5Characterization': [3116], 'IGFBP-3(1–87).': [3118], 'FLAG-tagged': [3122], '(15%)': [3128], 'anti-M2': [3134], '(B)': [3155], '125I-IGFs': [3157], '(C).View': [3158], '6Schematic': [3167], 'representation': [3168], '[1],': [3176], 'sequences': [3182], 'appropriate': [3185], 'structures': [3187], 'formed': [3188], '1–6.': [3205], '[2],': [3206], 'lacks': [3208], 'necessary': [3212], 'insulin;': [3222], 'bridges': [3226], 'produces': [3227], 'conducive': [3233], 'binding.': [3236, 3327], '[3,': [3237], '4],': [3238], 'when': [3239], 'fragmented,': [3246], 'NH2terminus': [3253], 'exposed,': [3259], 'resulting': [3260, 3591, 3768, 4006], 'IGFs.View': [3270], 'next': [3280], 'investigated': [3281], 'biological': [3283], 'relevance': [3284, 3803], 'assays': [3293], 'IGFBP-7.': [3314, 4404], '300': [3321, 3350], 'pmol,': [3322, 3346], 'did': [3323, 3552], 'block': [3325], 'inhibited,': [3339], 'however,': [3340], '(60%': [3343], '90%': [3348], 'pmol)': [3351], '7),': [3353], 'compete': [3358, 4408], 'Inhibition': [3366], 'confirmed': [3377], '(data': [3382], 'shown).': [3384], 'Thus,': [3385, 3825], '100–300': [3386], 'inhibit': [3393, 3522, 3584, 3997], 'membranes.': [3398, 3527], 'discrepancy': [3400], 'action': [3405], 'latter': [3413], '1.': [3421], 'care': [3423], 'exercised': [3426], 'estimating': [3428], 'experiments,': [3432], 'it': [3433, 3660], 'likely': [3435], 'more': [3440], 'effectively': [3441], 'does': [3443], 'exhibited': [3451], 'receptor.': [3455], 'pathways,': [3464, 3723], 'IRS-1': [3470, 3533, 3558, 3565, 4011], 'phosphorylation,': [3471], 'tested.': [3473], 'blunted': [3477], 'manner,': [3489], '55': [3491], '80%': [3493], 'respectively': [3504, 3546], '8': [3506, 3548], 'ineffective': [3510], 'concentrations,': [3513], 'predicted': [3515], 'inability': [3518], 'Similarly,': [3528], 'inhibited': [3535, 3704], '65': [3536], '85%': [3538], 'differences': [3551], 'among': [3559], 'tested,': [3561], 'immunoblots.': [3566], 'Current': [3608], 'proposes': [3610], 'major': [3613], 'difference': [3614], 'affinity.': [3632], 'addition,': [3634], '5–25-fold': [3651], 'do': [3655], 'IGFBPs.': [3658], 'play': [3668, 3690], 'roles': [3669], 'regulating': [3671], 'IGFBP-1': [3674, 3688], 'production': [3675], 'suppressed': [3677], 'carbohydrate': [3681], 'stimulated': [3683], 'hypoglycemia,': [3685], 'counterregulatory': [3692], 'role': [3693], 'glucose': [3695], 'homeostasis.': [3696], 'Proteolyzed': [3697], 'fragments,': [3699, 3782], 'proteolyzed': [3712], 'regulate': [3720, 3746], 'despite': [3724], 'having': [3725], 'present': [3733, 3789], 'studies,': [3734], 'tested': [3737], 'fragmented': [3761], 'Our': [3775], 'generated': [3784], 'plasmin': [3786], 'digestion': [3787], 'normal': [3791], 'urine,': [3793, 4044], 'affinity,': [3799], 'supporting': [3800], 'physiological': [3802], '2P.': [3810], 'Vorwerk,': [3811], 'Yamanaka,': [3813], 'Spagnoli,': [3815], 'Oh,': [3817], 'Rosenfeld,': [3821], 'submitted': [3822], 'publication.': [3824], 'recent': [3826], 'current': [3832], 'view': [3833], 'observations:': [3842], '1)': [3843], 'proteolysis': [3845, 3986], 'peptide': [3848, 4413], 'Scholar);': [3889, 3957], '2)': [3890], 'existence': [3901], '3)': [3958], '4)': [3991], 'can,': [3993], 'certain': [3995], 'conditions,': [3996, 4100], 'reduce': [4004], 'stimulation': [4007], 'phosphorylation.': [4012], 'Immunoblot': [4013], 'antibodies': [4016], 'conditioned': [4030], 'number': [4034], 'lines,': [4037], 'cerebrospinal': [4042], 'fluid,': [4043, 4046], 'Quantitative': [4067], 'await': [4069], 'development': [4071], 'radioimmunoassays.': [4073], 'Proteolytic': [4074], 'originally': [4084], 'pregnancy': [4087], 'wide': [4096], 'variety': [4097], 'clinical': [4099], 'critically': [4102], 'ill': [4103], 'patients,': [4104], 'patients': [4105], 'catabolic': [4107], 'disease,': [4108], 'noninsulin-dependent': [4112], 'mellitus': [4114], '33Bang': [4150], 'Brismar': [4152], '78:': [4161, 4340], '1119-1127Crossref': [4162], '(92)': [4165], '34Bereket': [4168], 'Lang': [4170], 'C.H.': [4171], 'Blethen': [4172], 'S.L.': [4173], 'Gelato': [4174], 'M.C.': [4175], 'Fan': [4176], 'Frost': [4178], 'R.A.': [4179], 'T.A.': [4181], '80:': [4187], '1312-1317Crossref': [4188], '35Fielder': [4192], 'P.J.': [4193], 'Thordarson': [4194], 'Talamantes': [4196], '127:': [4202], '2270-2280Crossref': [4203], '(72)': [4206], '36Hossenlopp': [4209], 'Segovia': [4211], 'Roghani': [4215], 'Bredon': [4217], '797-805Crossref': [4227], '(381)': [4230], '37Liu': [4233], 'Baxter': [4235], '1992;': [4243], '75:': [4244], '1261-1267Crossref': [4245], '(17)': [4248], '38Rutishauser': [4251], 'Schmid': [4253], 'Hauri': [4255], 'Froesch': [4257], 'E.R.': [4258], 'Zapf': [4259], 'FEBS': [4261], 'Lett.': [4262], '334:': [4264], '23-26Crossref': [4265], '(21)': [4268], 'Many': [4271], 'diseases': [4274], 'varying': [4281], 'degrees,': [4282], 'measured': [4284], 'activity': [4291], 'defective': [4293], '(39Freidenberg': [4297], 'G.R.': [4298], 'Reichart': [4299], 'Olefsky': [4301], 'J.M.': [4302], 'Henry': [4303], 'R.R.': [4304], 'Invest.': [4307, 4338], '1398-1406Crossref': [4310], '(170)': [4313], '40Caro': [4316], 'J.F.': [4317, 4331], 'Ittoop': [4318], 'O.': [4319], 'Pories': [4320], 'W.J.': [4321], 'Meelheim': [4322], 'Flickinger': [4324], 'E.G.': [4325], 'Thomas': [4326], 'Jenquin': [4328], 'Silverman': [4330], 'Khazanie': [4332], 'P.G.': [4333], 'Sinha': [4334], '249-258Crossref': [4341], '(185)': [4344], '41Arner': [4347], 'Pollare': [4349], 'Lithell': [4351], 'Livingston': [4353], 'J.N.': [4354], 'Diabetologia.': [4355], '1987;': [4356], '30:': [4357], '437-440Crossref': [4358], '(164)': [4361], '42Haring': [4364], 'Obermaier-Kusser': [4366], 'Diabetes': [4368], '5:': [4372], '431-441Crossref': [4373], '(25)': [4376], 'tempting': [4381], 'speculate': [4383], 'sequester': [4418], 'receptors.': [4423], 'observations': [4425], 'support': [4427], 'novel': [4429], 'interactions': [4433], 'approach': [4445], 'understanding': [4448], 'pathophysiology': [4451], 'resistance.': [4454], 'thank': [4456], 'Rotwein,': [4458], 'critical': [4468], 'comments,': [4469], 'Oda': [4472], 'technical': [4474], 'advice.': [4475]}, 'cited_by_api_url': 'https://api.openalex.org/works?filter=cites:W2062465228', 'counts_by_year': [{'year': 2024, 'cited_by_count': 9}, {'year': 2023, 'cited_by_count': 6}, {'year': 2022, 'cited_by_count': 7}, {'year': 2021, 'cited_by_count': 8}, {'year': 2020, 'cited_by_count': 10}, {'year': 2019, 'cited_by_count': 13}, {'year': 2018, 'cited_by_count': 8}, {'year': 2017, 'cited_by_count': 9}, {'year': 2016, 'cited_by_count': 7}, {'year': 2015, 'cited_by_count': 11}, {'year': 2014, 'cited_by_count': 3}, {'year': 2013, 'cited_by_count': 12}, {'year': 2012, 'cited_by_count': 5}], 'updated_date': '2025-01-12T20:28:33.251963', 'created_date': '2016-06-24'}
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