title: Insulin-like growth factor-I regulation of immune function: a potential therapeutic target in autoimmune diseases?
abstract: This topically limited review explores the relationship between the immune system and insulin-like growth factors (IGF-I and IGF-II) and the proteins through which they act, including IGF-I receptor (IGF-IR) and the IGF-I binding proteins. The IGF/IGF-IR pathway plays important and diverse roles in tissue development and function. It regulates cell cycle progression, apoptosis, and the translation of proteins. Many of the consequences ascribed to IGF-IR activation result from its association with several accessory proteins that are either identical or closely related to those involved in insulin receptor signaling. Relatively recent awareness that IGF-I and IGF-IR regulate immune function has cast this pathway in an unexpected light; it may represent an important switch governing the quality and amplitude of immune responses. IGF-I/IGF-IR signaling may also participate in the pathogenesis of autoimmune diseases, although its relationship with these processes seems complex and relatively unexplored. On the one hand, IGF-I seems to protect experimental animals from developing insulin-deficient diabetes mellitus. In contrast, activating antibodies directed at IGF-IR have been detected in patients with Graves' disease, where the receptor is overexpressed by multiple cell types. The frequency of IGF-IR+ B and T cells is substantially increased in patients with that disease. Potential involvement of IGF-I and IGF-IR in the pathogenesis of autoimmune diseases suggests that this pathway might constitute an attractive therapeutic target. IGF-IR has been targeted in efforts directed toward drug development for cancer, employing both small-molecule and monoclonal antibody approaches. These have been generally well-tolerated. Recognizing the broader role of IGF-IR in regulating both normal and pathological immune responses may offer important opportunities for therapeutic intervention in several allied diseases that have proven particularly difficult to treat.
authors.affiliation: Department of Ophthalmology and Visual Sciences, Kellogg Eye Center, University of Michigan Medical School, 1000 Wall Street, Ann Arbor, MI 48105, USA. terrysmi@med.umich.edu
authors.forename: Terry J
authors.initials: TJ
authors.lastname: Smith
mesh_terms: D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000737:chemistry / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000502:physiology*; D017526:Receptor, IGF Type 1 / Q000737:chemistry / Q000378:metabolism
chemical_list: D018970:Insulin-Like Growth Factor Binding Protein 1; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1
references.citation: Gastroenterology. 2005 May;128(5):1278-91
references.pmid: 15887111
references.citation: Endocr Rev. 1994 Feb;15(1):5-26
references.pmid: 8156939
references.citation: J Clin Invest. 1998 Jun 1;101(11):2301-8
references.pmid: 9616201
references.citation: Biochem Biophys Res Commun. 1993 Jun 30;193(3):1216-23
references.pmid: 8323544
references.citation: J Immunol. 1999 Apr 1;162(7):4293-9
references.pmid: 10201961
references.citation: Cell Immunol. 1998 Feb 1;183(2):157-61
references.pmid: 9607000
references.citation: Atherosclerosis. 2007 Jul;193(1):142-50
references.pmid: 16842799
references.citation: Thyroid. 1993 Winter;3(4):297-300
references.pmid: 7509671
references.citation: Endocrinology. 2005 Feb;146(2):835-44
references.pmid: 15542454
references.citation: Cell Mol Life Sci. 2000 Jul;57(7):1050-93
references.pmid: 10961344
references.citation: Blood. 2004 Mar 15;103(6):2291-8
references.pmid: 14592826
references.citation: Nature. 2007 Oct 4;449(7162):564-9
references.pmid: 17873860
references.citation: Blood. 2006 Jan 15;107(2):669-78
references.pmid: 16166596
references.citation: Transplantation. 1991 Nov;52(5):879-84
references.pmid: 1949174
references.citation: Clin Exp Immunol. 1995 Nov;102(2):335-40
references.pmid: 7586687
references.citation: Genetics. 2007 Sep;177(1):549-56
references.pmid: 17603103
references.citation: Proc Natl Acad Sci U S A. 1992 May 15;89(10):4481-5
references.pmid: 1584780
references.citation: J Clin Endocrinol Metab. 1996 Jun;81(6):2257-63
references.pmid: 8964861
references.citation: J Immunol. 2003 Jun 15;170(12):6348-54
references.pmid: 12794168
references.citation: Blood. 1994 Mar 15;83(6):1569-74
references.pmid: 8123847
references.citation: Endocrinology. 1990 Jan;126(1):299-306
references.pmid: 2293990
references.citation: J Exp Med. 1999 Aug 16;190(4):479-86
references.pmid: 10449519
references.citation: Acta Endocrinol (Copenh). 1983 Jan;102(1):21-6
references.pmid: 6681686
references.citation: J Biol Chem. 1993 Feb 5;268(4):2655-61
references.pmid: 7679099
references.citation: Am J Physiol Gastrointest Liver Physiol. 2000 Dec;279(6):G1307-22
references.pmid: 11093955
references.citation: J Biol Chem. 1975 Dec 10;250(23):8990-6
references.pmid: 391
references.citation: Endocrinology. 2006 Jun;147(6):2616-8
references.pmid: 16707730
references.citation: Exp Hematol. 1994 Dec;22(13):1273-7
references.pmid: 7957713
references.citation: J Immunol. 1995 Jun 1;154(11):5736-45
references.pmid: 7751625
references.citation: J Biol Chem. 1999 Apr 16;274(16):11408-16
references.pmid: 10196234
references.citation: Horm Metab Res. 2003 Nov-Dec;35(11-12):843-9
references.pmid: 14710367
references.citation: Endocr Res. 1984;10(2):101-12
references.pmid: 6389104
references.citation: J Clin Endocrinol Metab. 1995 Sep;80(9):2620-5
references.pmid: 7673404
references.citation: Clin Cancer Res. 2007 Sep 15;13(18 Pt 2):5549s-5555s
references.pmid: 17875788
references.citation: Histochem J. 1996 Dec;28(12):835-57
references.pmid: 9015706
references.citation: Immunology. 1995 Jul;85(3):394-9
references.pmid: 7558127
references.citation: Leukemia. 2007 May;21(5):886-96
references.pmid: 17361225
references.citation: FEBS Lett. 1982 Nov 22;149(1):105-8
references.pmid: 6759171
references.citation: Acta Endocrinol (Copenh). 1991 Jun;124(6):707-14
references.pmid: 1712529
references.citation: Growth Horm IGF Res. 2005 Aug;15(4):265-74
references.pmid: 16005252
references.citation: Blood. 1992 Sep 15;80(6):1443-7
references.pmid: 1520871
references.citation: Mol Cell Neurosci. 1994 Oct;5(5):418-30
references.pmid: 7529631
references.citation: Am J Pathol. 2008 Sep;173(3):600-9
references.pmid: 18688037
references.citation: J Clin Endocrinol Metab. 1995 Apr;80(4):1179-83
references.pmid: 7536201
references.citation: Mol Pathol. 2002 Feb;55(1):46-54
references.pmid: 11836447
references.citation: J Immunol. 1987 Apr 1;138(7):2100-3
references.pmid: 3549897
references.citation: Am J Pathol. 2003 Jan;162(1):3-6
references.pmid: 12507883
references.citation: Endocr Rev. 1997 Dec;18(6):801-31
references.pmid: 9408744
references.citation: J Biol Chem. 1993 Nov 5;268(31):23435-40
references.pmid: 7693688
references.citation: Arthritis Rheum. 1989 Jan;32(1):66-71
references.pmid: 2912464
references.citation: Immunol Today. 2000 Apr;21(4):192-9
references.pmid: 10740243
references.citation: J Biol Chem. 1998 Mar 13;273(11):6074-9
references.pmid: 9497324
references.citation: J Cell Sci. 1982 Oct;57:129-37
references.pmid: 6891385
references.citation: J Clin Invest. 1994 Jul;94(1):293-300
references.pmid: 7518833
references.citation: Biochem Biophys Res Commun. 1991 Aug 30;179(1):495-501
references.pmid: 1715697
references.citation: Biochem Biophys Res Commun. 1993 Oct 15;196(1):92-8
references.pmid: 8216340
references.citation: J Rheumatol. 1995 Feb;22(2):275-81
references.pmid: 7738951
references.citation: Growth Regul. 1992 Jun;2(2):69-79
references.pmid: 1283100
references.citation: Clin Cancer Res. 2005 Mar 1;11(5):2063-73
references.pmid: 15756033
references.citation: J Clin Endocrinol Metab. 2004 Oct;89(10):5076-80
references.pmid: 15472208
references.citation: Cancer Cell. 2002 Mar;1(2):117-23
references.pmid: 12086869
references.citation: Clin Dev Immunol. 2005 Mar;12(1):47-58
references.pmid: 15712599
references.citation: Bioorg Med Chem Lett. 2007 Feb 15;17(4):1091-7
references.pmid: 17127062
references.citation: J Biol Chem. 1995 Nov 24;270(47):28289-96
references.pmid: 7499327
references.citation: Endocr Rev. 1997 Apr;18(2):157-79
references.pmid: 9101135
references.citation: Nat Genet. 2008 Jun;40(6):713-5
references.pmid: 18438405
references.citation: Endocrinology. 1987 Nov;121(5):1784-8
references.pmid: 2959469
references.citation: J Clin Invest. 1988 Mar;81(3):791-7
references.pmid: 2963830
references.citation: Cancer Res. 2006 Feb 15;66(4):2391-402
references.pmid: 16489046
references.citation: J Clin Endocrinol Metab. 1995 Dec;80(12):3732-8
references.pmid: 8530626
references.citation: Nat Genet. 2002 May;31(1):111-5
references.pmid: 11923875
references.citation: Int J Biochem Cell Biol. 1995 Oct;27(10):987-94
references.pmid: 7497000
references.citation: Biogerontology. 2002;3(1-2):19-24
references.pmid: 12014835
references.citation: Endocr Rev. 2007 Feb;28(1):20-47
references.pmid: 16931767
references.citation: Nat Rev Cancer. 2008 Dec;8(12):915-28
references.pmid: 19029956
references.citation: J Immunol. 2007 Mar 1;178(5):3281-7
references.pmid: 17312178
references.citation: J Biol Chem. 1997 Dec 5;272(49):30822-7
references.pmid: 9388225
references.citation: Mol Endocrinol. 2000 Mar;14(3):440-8
references.pmid: 10707961
references.citation: Endocr Rev. 1999 Dec;20(6):761-87
references.pmid: 10605625
references.citation: Diabetes. 2006 Dec;55(12):3246-55
references.pmid: 17130467
references.citation: Endocrinology. 1998 Oct;139(10):4120-6
references.pmid: 9751491
references.citation: Pediatr Res. 1987 Sep;22(3):286-91
references.pmid: 3309859
references.citation: J Leukoc Biol. 2004 Nov;76(5):1019-27
references.pmid: 15316031
references.citation: Mol Endocrinol. 1996 Jun;10(6):631-41
references.pmid: 8776723
references.citation: J Endocrinol. 2002 Oct;175(1):33-40
references.pmid: 12379488
references.citation: Curr Opin Drug Discov Devel. 2008 Mar;11(2):178-85
references.pmid: 18283605
references.citation: Mol Endocrinol. 2000 May;14(5):662-70
references.pmid: 10809230
references.citation: Dev Dyn. 2002 Mar;223(2):273-84
references.pmid: 11836791
references.citation: J Cell Biol. 1998 Mar 9;140(5):1055-62
references.pmid: 9490719
references.citation: Cancer Epidemiol Biomarkers Prev. 2004 Jan;13(1):163-5
references.pmid: 14744750
references.citation: Autoimmun Rev. 2007 Nov;7(1):1-7
references.pmid: 17967717
references.citation: Annu Rev Biochem. 1992;61:307-30
references.pmid: 1323236
references.citation: Curr Opin Cell Biol. 1999 Apr;11(2):184-9
references.pmid: 10209149
references.citation: Chest. 2002 Dec;122(6 Suppl):289S-293S
references.pmid: 12475802
references.citation: Int J Biochem Cell Biol. 1997 Nov;29(11):1231-4
references.pmid: 9451819
references.citation: Eur J Immunol. 2000 Apr;30(4):1010-8
references.pmid: 10760788
references.citation: Endocrinology. 2007 May;148(5):2532-41
references.pmid: 17289850
references.citation: Proc Natl Acad Sci U S A. 1994 Jan 4;91(1):123-7
references.pmid: 8278351
references.citation: J Clin Invest. 1981 Jun;67(6):1636-42
references.pmid: 6787080
references.citation: Clin Endocrinol (Oxf). 1998 Oct;49(4):483-9
references.pmid: 9876346
references.citation: Biochem J. 1989 Feb 15;258(1):267-72
references.pmid: 2539101
references.citation: J Clin Endocrinol Metab. 1996 Jan;81(1):150-5
references.pmid: 8550744
references.citation: J Biol Chem. 2000 Jul 21;275(29):22583-9
references.pmid: 10807918
references.citation: Science. 1996 Nov 15;274(5290):1194-7
references.pmid: 8895468
references.citation: Arch Physiol Biochem. 2008 Feb;114(1):23-37
references.pmid: 18465356
references.citation: Autoimmunity. 2003 Sep-Nov;36(6-7):417-21
references.pmid: 14669950
references.citation: Clin Exp Pharmacol Physiol. 2008 Jul;35(7):846-51
references.pmid: 18215180
references.citation: J Biol Chem. 1996 Jun 7;271(23):13523-9
references.pmid: 8662813
references.citation: Nat Rev Drug Discov. 2002 Oct;1(10):769-83
references.pmid: 12360255
references.citation: Biochem J. 2007 Oct 1;407(1):79-87
references.pmid: 17600529
references.citation: Proc Natl Acad Sci U S A. 1986 Feb;83(3):822-6
references.pmid: 3511475
references.citation: Eur J Med Genet. 2007 Jan-Feb;50(1):1-10
references.pmid: 17056309
references.citation: J Biol Chem. 2000 Oct 27;275(43):33607-13
references.pmid: 10874028
references.citation: Nat Rev Drug Discov. 2007 Oct;6(10):821-33
references.pmid: 17906644
references.citation: Scand J Immunol. 2002 May;55(5):442-52
references.pmid: 11975755
references.citation: J Biol Chem. 1999 Jul 16;274(29):20281-6
references.pmid: 10400647
references.citation: Endocrine. 1998 Oct;9(2):185-92
references.pmid: 9867252
references.citation: J Endocrinol. 2006 Jun;189(3):605-15
references.pmid: 16731791
references.citation: EMBO J. 1997 Jun 16;16(12):3693-704
references.pmid: 9218810
references.citation: J Biol Chem. 1993 Jul 15;268(20):14964-71
references.pmid: 7686909
references.citation: J Invest Dermatol. 1987 Jul;89(1):100-4
references.pmid: 3496398
references.citation: Lab Invest. 1984 Jun;50(6):608-35
references.pmid: 6202955
references.citation: Clin Cancer Res. 2001 Jul;7(7):2134-44
references.pmid: 11448933
references.citation: Genomics. 1999 Jul 1;59(1):66-76
references.pmid: 10395801
references.citation: Clin Exp Immunol. 1971 Aug;9(2):209-25
references.pmid: 4936804
references.citation: Curr Opin Struct Biol. 2007 Dec;17(6):699-705
references.pmid: 17851071
references.citation: Endocrinology. 2001 Dec;142(12):5131-9
references.pmid: 11713206
references.citation: J Biol Chem. 2009 Apr 10;284(15):10254-67
references.pmid: 19211557
references.citation: Endocrinology. 2002 Nov;143(11):4259-64
references.pmid: 12399420
references.citation: J Biol Chem. 2002 May 31;277(22):19448-54
references.pmid: 11940579
references.citation: Mol Endocrinol. 2005 Jan;19(1):1-11
references.pmid: 15528274
references.citation: J Endocrinol. 2008 Oct;199(1):69-80
references.pmid: 18653623
references.citation: Lancet. 1993 Aug 7;342(8867):337-8
references.pmid: 8101586
references.citation: Science. 1993 Sep 17;261(5128):1591-4
references.pmid: 8372354
references.citation: Trends Endocrinol Metab. 1994 Mar;5(2):60-4
references.pmid: 18407189
references.citation: Endocrinology. 2005 May;146(5):2473-80
references.pmid: 15705774
references.citation: Int J Cancer. 2005 Jan 10;113(2):316-28
references.pmid: 15386423
references.citation: Crit Care Med. 1996 Sep;24(9):1460-6
references.pmid: 8797616
references.citation: J Mol Endocrinol. 2002 Jun;28(3):207-12
references.pmid: 12063186
references.citation: J Clin Invest. 2002 Oct;110(7):1011-9
references.pmid: 12370279
references.citation: J Immunol. 2008 Sep 15;181(6):4397-405
references.pmid: 18768899
references.citation: Mol Endocrinol. 1994 Jan;8(1):40-50
references.pmid: 7512194
references.citation: Mol Genet Metab. 1999 Oct;68(2):161-81
references.pmid: 10527667
references.citation: Endocrinology. 1988 Jan;122(1):127-32
references.pmid: 2446854
references.citation: J Rheumatol. 2001 Jan;28(1):12-21
references.pmid: 11196512
references.citation: Mol Endocrinol. 2003 Sep;17(9):1824-33
references.pmid: 12791772
references.citation: Arthritis Rheum. 2002 May;46(5):1139-54
references.pmid: 12115215
references.citation: Nature. 2007 Jul 26;448(7152):427-34
references.pmid: 17653185
references.citation: J Biol Chem. 2000 Dec 8;275(49):38371-7
references.pmid: 10967115
references.citation: Nature. 2003 Jan 9;421(6919):182-7
references.pmid: 12483226
references.citation: J Endocrinol. 1995 Nov;147(2):203-9
references.pmid: 7490549
references.citation: J Immunol. 2007 Sep 1;179(5):3351-61
references.pmid: 17709552
references.citation: Rheumatol Int. 1997;17(1):29-37
references.pmid: 9194211
references.citation: Endocrinology. 2006 Jun;147(6):2619-30
references.pmid: 16513827
references.citation: Growth Horm IGF Res. 2001 Dec;11(6):364-7
references.pmid: 11914023
references.citation: Horm Metab Res. 2003 Nov-Dec;35(11-12):751-7
references.pmid: 14710354
references.citation: J Leukoc Biol. 2004 Oct;76(4):862-7
references.pmid: 15277570
references.citation: Growth Horm IGF Res. 2009 Apr;19(2):136-45
references.pmid: 18809348
references.citation: J Biol Chem. 1978 Apr 25;253(8):2769-76
references.pmid: 632300
references.citation: Cancer Res. 2003 Aug 15;63(16):5073-83
references.pmid: 12941837
references.citation: J Cell Biol. 1999 Aug 23;146(4):697-702
references.pmid: 10459005
references.citation: J Immunol. 1997 Jul 1;159(1):487-96
references.pmid: 9200490
references.citation: J Immunol. 2004 Mar 1;172(5):2803-10
references.pmid: 14978080
references.citation: J Immunol. 2003 Jun 1;170(11):5583-9
references.pmid: 12759437
references.citation: Oncologist. 2009 Jan;14(1):83-91
references.pmid: 19126579
references.citation: Nature. 1993 Dec 2;366(6454):461-4
references.pmid: 8247153
references.citation: Growth Horm IGF Res. 2009 Oct;19(5):420-5
references.pmid: 19138871
references.citation: Circ Res. 2003 Nov 14;93(10):925-31
references.pmid: 14563713
references.citation: Blood. 1993 Nov 15;82(10):3005-11
references.pmid: 7693033
references.citation: Genetics. 2006 Mar;172(3):1655-63
references.pmid: 16322502
references.citation: Ann Surg. 2000 Feb;231(2):246-52
references.pmid: 10674617
references.citation: Blood. 1992 Sep 1;80(5):1207-12
references.pmid: 1515639
references.citation: Biochem J. 1989 May 1;259(3):665-71
references.pmid: 2730580
references.citation: Curr Opin Clin Nutr Metab Care. 2002 Jul;5(4):371-5
references.pmid: 12107371
references.citation: Biochem J. 1999 Sep 15;342 Pt 3:615-23
references.pmid: 10477272
references.citation: Genetics. 1995 Dec;141(4):1399-406
references.pmid: 8601482
references.citation: Nat Genet. 2008 Jun;40(6):710-2
references.pmid: 18438406
references.citation: Transplantation. 2003 Jun 27;75(12):1977-83
references.pmid: 12829897
references.citation: Leukemia. 2006 Jul;20(7):1254-60
references.pmid: 16642049
references.citation: Neuroendocrinology. 2002 Feb;75(2):139-50
references.pmid: 11867942
references.citation: Nat Rev Endocrinol. 2009 Apr;5(4):219-26
references.pmid: 19352320
references.citation: Endocr Rev. 2002 Dec;23(6):824-54
references.pmid: 12466191
references.citation: Nature. 1978 Jul 6;274(5666):62-3
references.pmid: 26882
references.citation: Cancer Res. 1998 Jul 15;58(14):3021-7
references.pmid: 9679966
references.citation: J Immunol. 1993 Aug 15;151(4):1811-20
references.pmid: 7688386
references.citation: FEBS Lett. 2004 May 7;565(1-3):19-22
references.pmid: 15135045
references.citation: J Clin Endocrinol Metab. 1986 Sep;63(3):730-5
references.pmid: 3016022
references.citation: J Biol Chem. 1997 Oct 10;272(41):25706-12
references.pmid: 9325295
references.citation: Mech Ageing Dev. 1997 Feb;93(1-3):47-57
references.pmid: 9089570
references.citation: J Clin Invest. 1988 Nov;82(5):1685-93
references.pmid: 3183063
references.citation: Brain Behav Immun. 1992 Dec;6(4):377-86
references.pmid: 1490031
references.citation: Ann N Y Acad Sci. 1992 Dec 26;673:231-9
references.pmid: 1485720
references.citation: Endocrinology. 2004 Feb;145(2):627-38
references.pmid: 14617576
references.citation: Horm Res. 1994;41 Suppl 2:56-64; discussion 65
references.pmid: 8088705
references.citation: Am J Respir Cell Mol Biol. 1991 May;4(5):432-9
references.pmid: 1850606
references.citation: Nature. 1990 Oct 18;347(6294):669-71
references.pmid: 1699135
references.citation: Biochemistry. 2002 Jul 30;41(30):9389-97
references.pmid: 12135360
references.citation: Cancer. 1997 May 1;79(9):1828-39
references.pmid: 9129003
references.citation: J Biol Chem. 2002 Sep 27;277(39):36740-7
references.pmid: 12101187
references.citation: Endocrinology. 1987 Apr;120(4):1439-48
references.pmid: 3549261
references.citation: Nature. 1993 May 6;363(6424):45-51
references.pmid: 8479536
references.citation: Endocrinology. 2002 Apr;143(4):1206-12
references.pmid: 11897674
references.citation: Curr Dir Autoimmun. 2003;6:89-104
references.pmid: 12408048
references.citation: Gene Ther. 2000 Dec;7(23):2015-22
references.pmid: 11175313
references.citation: Ann N Y Acad Sci. 1998 Apr 15;842:76-81
references.pmid: 9599296
references.citation: Nat Rev Immunol. 2008 Jun;8(6):458-66
references.pmid: 18500230
references.citation: Endocrinology. 2000 Mar;141(3):1209-17
references.pmid: 10698198
references.citation: Br J Dermatol. 2008 Jul;159(1):86-90
references.pmid: 18489607
references.citation: Biochem Mol Med. 1996 Jun;58(1):31-6
references.pmid: 8809343
references.citation: J Immunol. 2003 Oct 1;171(7):3550-9
references.pmid: 14500651
references.citation: J Recept Res. 1983;3(4):481-94
references.pmid: 6358488
references.citation: Blood. 2003 Aug 15;102(4):1428-34
references.pmid: 12714521
references.citation: Gastroenterology. 2005 Jul;129(1):185-203
references.pmid: 16012947
references.citation: J Clin Invest. 1992 Aug;90(2):439-46
references.pmid: 1322940
references.citation: Cell. 1993 Oct 8;75(1):59-72
references.pmid: 8402901
references.citation: AJR Am J Roentgenol. 1987 Aug;149(2):269-72
references.pmid: 3496749
references.citation: J Immunol. 2004 Sep 1;173(5):3564-9
references.pmid: 15322222
references.citation: Curr Opin Cell Biol. 1998 Aug;10(4):504-12
references.pmid: 9719872
references.citation: J Neurosci. 1992 Dec;12(12):4737-44
references.pmid: 1281494
references.citation: J Immunol. 2000 Aug 1;165(3):1331-6
references.pmid: 10903734
references.citation: Cancer Cell. 2004 Mar;5(3):221-30
references.pmid: 15050914
references.citation: J Clin Endocrinol Metab. 2000 Dec;85(12):4758-64
references.pmid: 11134139
references.citation: Am Rev Respir Dis. 1991 Sep;144(3 Pt 1):706-13
references.pmid: 1892314
references.citation: J Immunol. 2008 Oct 15;181(8):5768-74
references.pmid: 18832736
references.citation: Nat Rev Rheumatol. 2009 Aug;5(8):433-41
references.pmid: 19581902
references.citation: Endocr Rev. 2003 Dec;24(6):802-35
references.pmid: 14671007
references.citation: Diabetologia. 1997 Jul;40 Suppl 2:S2-17
references.pmid: 9248696
references.citation: Proc Natl Acad Sci U S A. 1972 Sep;69(9):2604-8
references.pmid: 4341701
references.citation: J Clin Endocrinol Metab. 2002 Jan;87(1):385-92
references.pmid: 11788681
references.citation: Endocrinology. 1990 Nov;127(5):2298-306
references.pmid: 1699745
references.citation: Clin Exp Immunol. 1994 Feb;95(2):337-42
references.pmid: 8306510
references.citation: Proc Natl Acad Sci U S A. 1996 Feb 6;93(3):1113-8
references.pmid: 8577724
references.citation: Arthritis Rheum. 1996 Sep;39(9):1556-65
references.pmid: 8814068
references.citation: Cancer Res. 2003 Jul 15;63(14):3991-4
references.pmid: 12873996
references.citation: Horm Res. 2003;59(6):276-80
references.pmid: 12784091
references.citation: Oncogene. 2004 Jul 1;23(30):5161-74
references.pmid: 15122317
references.citation: Nat Genet. 1999 Sep;23(1):32-40
references.pmid: 10471495
references.citation: Mol Cancer Ther. 2007 Aug;6(8):2158-67
references.pmid: 17671083
references.citation: J Biol Chem. 1999 Mar 12;274(11):6935-45
references.pmid: 10066747
references.citation: Science. 1971 Dec 10;174(4014):1137-9
references.pmid: 5133731
references.citation: J Clin Invest. 1990 Feb;85(2):448-55
references.pmid: 1688884
references.citation: Autoimmunity. 1993;16(4):251-7
references.pmid: 7517705
references.citation: Am J Pathol. 2006 Sep;169(3):954-66
references.pmid: 16936269
references.citation: J Immunol. 1981 Apr;126(4):1249-54
references.pmid: 7009735
references.citation: Cell Immunol. 2008 Mar-Apr;252(1-2):91-110
references.pmid: 18325486
references.citation: Endocrinology. 1987 Feb;120(2):785-90
references.pmid: 2948816
references.citation: Endocrinology. 1993 Oct;133(4):1525-31
references.pmid: 7691578
references.citation: J Clin Invest. 1993 Aug;92(2):540-8
references.pmid: 8349796
references.citation: J Immunol. 1994 May 1;152(9):4320-7
references.pmid: 8157955
references.citation: Proc Natl Acad Sci U S A. 1996 Mar 19;93(6):2482-7
references.pmid: 8637900
references.citation: Endocrinology. 1986 Aug;119(2):940-2
references.pmid: 2874015
references.citation: J Immunol. 2006 Sep 15;177(6):4218-23
references.pmid: 16951388
references.citation: Biochemistry. 1997 Apr 8;36(14):4108-17
references.pmid: 9100004
references.citation: Exp Hematol. 2006 Apr;34(4):508-18
references.pmid: 16569597
references.citation: Endocrinology. 1997 Jun;138(6):2280-5
references.pmid: 9165012
references.citation: Growth Horm IGF Res. 2000 Apr;10 Suppl A:S16-7
references.pmid: 10984276
references.citation: Annu Rev Cell Dev Biol. 1996;12:575-625
references.pmid: 8970738
references.citation: Immunity. 2002 Jun;16(6):769-77
references.pmid: 12121659
references.citation: Genes Dev. 1997 Sep 1;11(17):2239-49
references.pmid: 9303539
references.citation: J Immunol. 1992 Jan 1;148(1):63-71
references.pmid: 1345791
references.citation: Horm Res. 2004;61(4):159-64
references.pmid: 14691340
references.citation: Am J Physiol Cell Physiol. 2000 Aug;279(2):C335-40
references.pmid: 10912999
references.citation: J Clin Invest. 1994 May;93(5):2286-90
references.pmid: 7514194
references.citation: J Clin Endocrinol Metab. 1998 Jul;83(7):2445-9
references.pmid: 9661626
references.citation: Clin Sci (Lond). 1994 Feb;86(2):141-8
references.pmid: 8143424
references.citation: Science. 1989 Dec 22;246(4937):1620-2
references.pmid: 2556796
references.citation: J Clin Endocrinol Metab. 1994 Mar;78(3):635-41
references.pmid: 8126135
references.citation: J Clin Endocrinol Metab. 2000 Apr;85(4):1518-24
references.pmid: 10770191
references.citation: Endocrinology. 1998 Apr;139(4):1991-8
references.pmid: 9528986
references.citation: Blood. 2003 Oct 15;102(8):2933-9
references.pmid: 12842994
references.citation: J Clin Invest. 1988 Mar;81(3):879-84
references.pmid: 2893811
references.citation: Nat Rev Cancer. 2004 Jul;4(7):505-18
references.pmid: 15229476
references.citation: Mol Cell Biol. 1999 Jun;19(6):4008-18
references.pmid: 10330141
references.citation: Mol Endocrinol. 1995 Mar;9(3):350-60
references.pmid: 7776981
references.citation: Am J Respir Crit Care Med. 1998 Nov;158(5 Pt 1):1626-35
references.pmid: 9817718
references.citation: J Immunol. 1995 Aug 15;155(4):2123-33
references.pmid: 7636260
references.citation: J Biol Chem. 2001 Aug 31;276(35):33054-60
references.pmid: 11423532
references.citation: Stem Cells. 1998;16(3):193-9
references.pmid: 9617894
references.citation: J Immunol. 2005 May 1;174(9):5516-25
references.pmid: 15843550
references.citation: Endocrinology. 1988 Jan;122(1):133-6
references.pmid: 2826109
references.citation: N Engl J Med. 2002 May 30;346(22):1692-8
references.pmid: 12037148
references.citation: Oncogene. 2007 Apr 26;26(19):2678-84
references.pmid: 17072337
references.citation: Nat Rev Cancer. 2006 Sep;6(9):714-27
references.pmid: 16929325
references.citation: Nat Rev Mol Cell Biol. 2003 Mar;4(3):202-12
references.pmid: 12612639
references.citation: J Immunol. 2002 Jan 15;168(2):942-50
references.pmid: 11777993
references.citation: J Clin Invest. 1983 Nov;72(5):1801-13
references.pmid: 6630527
references.citation: Kidney Int. 2000 May;57(5):1991-2003
references.pmid: 10792618
references.citation: Cancer Res. 2004 Jan 1;64(1):236-42
references.pmid: 14729630
references.citation: Diabetes. 1989 Feb;38(2):152-8
references.pmid: 2644137
references.citation: Clin Endocrinol (Oxf). 1998 Apr;48(4):397-400
references.pmid: 9640404
references.citation: Immunology. 2002 Dec;107(4):461-71
references.pmid: 12460191
references.citation: J Endocrinol. 1992 Oct;135(1):135-45
references.pmid: 1279090
references.citation: Cancer Res. 1994 Jun 15;54(12):3179-85
references.pmid: 8205537
references.citation: J Clin Invest. 1995 May;95(5):2258-65
references.pmid: 7537760
references.citation: Adv Exp Med Biol. 1993;343:237-44
references.pmid: 7514337
references.citation: Proc Natl Acad Sci U S A. 1990 May;87(10):3690-4
references.pmid: 2187189
references.citation: J Biol Chem. 1996 Jun 21;271(25):14676-9
references.pmid: 8663298
references.citation: J Immunol. 2004 Apr 15;172(8):4661-5
references.pmid: 15067038
references.citation: J Clin Endocrinol Metab. 1991 May;72(5):1117-22
references.pmid: 1850753
references.citation: Biochem Biophys Res Commun. 2007 Jul 13;358(4):1136-41
references.pmid: 17524361
references.citation: Eur J Immunol. 1997 Oct;27(10):2495-501
references.pmid: 9368602
references.citation: AIDS. 2002 May 24;16(8):1103-11
references.pmid: 12004268
references.citation: Gut. 1993 Jul;34(7):944-7
references.pmid: 7688335
references.citation: Endocrinology. 1997 Dec;138(12):5630-6
references.pmid: 9389551
references.citation: EMBO J. 1998 Nov 16;17(22):6622-32
references.pmid: 9822606
references.citation: Proc Natl Acad Sci U S A. 1982 Feb;79(4):1286-90
references.pmid: 6461858
references.citation: FEBS Lett. 2002 Sep 11;527(1-3):293-7
references.pmid: 12220677
references.citation: Gastroenterology. 1986 Oct;91(4):830-6
references.pmid: 3743961
references.citation: J Clin Invest. 1993 Jun;91(6):2368-77
references.pmid: 8514850
references.citation: Autoimmun Rev. 2009 Jun;8(7):585-90
references.pmid: 19393204
references.citation: Prog Growth Factor Res. 1995;6(2-4):215-22
references.pmid: 8817664
references.citation: Crit Rev Immunol. 2001;21(4):323-37
references.pmid: 11922077
references.citation: Mol Cell Biol. 1990 Feb;10(2):464-73
references.pmid: 2153917
references.citation: Horm Res. 1996;45(1-2):38-45
references.pmid: 8742117
references.citation: J Exp Med. 1993 Jul 1;178(1):231-6
references.pmid: 8315380
references.citation: J Biol Chem. 2001 Nov 23;276(47):43980-6
references.pmid: 11500492
references.citation: Circ Res. 2001 May 25;88(10):1044-52
references.pmid: 11375274
references.citation: Endocr Rev. 1995 Feb;16(1):3-34
references.pmid: 7758431
references.citation: Clin Cancer Res. 1999 Jul;5(7):1935-44
references.pmid: 10430101
references.citation: Br J Cancer. 2009 Jan 27;100(2):366-9
references.pmid: 19165200
references.citation: Scand J Gastroenterol. 2007 Apr;42(4):464-70
references.pmid: 17454856
references.citation: J Biol Chem. 1998 Nov 27;273(48):32244-53
references.pmid: 9822703
references.citation: J Immunol. 1992 Dec 15;149(12):3851-7
references.pmid: 1460277
references.citation: Curr Opin Cell Biol. 1999 Apr;11(2):177-83
references.pmid: 10209148
references.citation: Mol Biol Cell. 1998 Sep;9(9):2383-92
references.pmid: 9725901
references.citation: Am J Physiol. 1998 Apr;274(4):R912-20
references.pmid: 9575951
references.citation: Arterioscler Thromb Vasc Biol. 1999 Sep;19(9):2119-26
references.pmid: 10479653
references.citation: Endocrinology. 2006 Apr;147(4):1941-9
references.pmid: 16410300
references.citation: AIDS. 1998 May 28;12(8):895-904
references.pmid: 9631143
references.citation: J Immunol. 1980 Feb;124(2):739-44
references.pmid: 6965389
references.citation: BMC Musculoskelet Disord. 2004 Oct 20;5(1):37
references.pmid: 15496230
references.citation: Nature. 1984 Aug 30-Sep 5;310(5980):781-4
references.pmid: 6382023
references.citation: Horm Metab Res. 1999 Feb-Mar;31(2-3):242-6
references.pmid: 10226808
references.citation: J Clin Endocrinol Metab. 1992 Jul;75(1):183-8
references.pmid: 1619008
references.citation: J Clin Endocrinol Metab. 2009 May;94(5):1797-802
references.pmid: 19240157
references.citation: Cancer Res. 2003 Dec 15;63(24):8912-21
references.pmid: 14695208
references.citation: J Exp Med. 1994 Aug 1;180(2):727-32
references.pmid: 8046348
references.citation: Adv Dent Res. 1996 Apr;10(1):44-6
references.pmid: 8934923
references.citation: J Clin Invest. 1988 Sep;82(3):950-7
references.pmid: 3262126
references.citation: J Mol Biol. 2009 Dec 18;394(5):878-92
references.pmid: 19835884
references.citation: Endocrinology. 2001 Jan;142(1):108-13
references.pmid: 11145572
references.citation: J Biol Chem. 1995 Jun 30;270(26):15639-43
references.pmid: 7541045
references.citation: Mol Endocrinol. 2004 Nov;18(11):2727-39
references.pmid: 15272055
references.citation: J Biol Chem. 2007 Sep 7;282(36):26150-7
references.pmid: 17620336
references.citation: Endocr Rev. 2009 Feb;30(1):51-74
references.pmid: 19075184
references.citation: Nat Med. 1997 Aug;3(8):917-21
references.pmid: 9256286
references.citation: J Neurosci. 1991 Nov;11(11):3442-55
references.pmid: 1658250
references.citation: J Cell Biochem. 2008 Feb 1;103(2):624-35
references.pmid: 17562544
references.citation: J Biol Chem. 1997 Nov 21;272(47):29460-7
references.pmid: 9368005
references.citation: J Biol Chem. 1989 Jul 5;264(19):11004-8
references.pmid: 2472386
references.citation: J Clin Endocrinol Metab. 1986 Jan;62(1):28-35
references.pmid: 2999181
references.citation: Endocr Rev. 1995 Apr;16(2):143-63
references.pmid: 7540132
references.citation: Shock. 2008 Jun;29(6):740-7
references.pmid: 18004231
references.citation: Infect Immun. 2008 Mar;76(3):935-41
references.pmid: 18160480
references.citation: J Cell Physiol. 2005 May;203(2):328-34
references.pmid: 15700281
references.citation: Endocrinology. 2007 Feb;148(2):903-11
references.pmid: 17122083
references.citation: Mol Cancer Ther. 2007 Apr;6(4):1357-67
references.pmid: 17431114
references.citation: Rheumatology (Oxford). 2002 Mar;41(3):352-3
references.pmid: 11934980
references.citation: Annu Rev Immunol. 1989;7:111-43
references.pmid: 2653368
references.citation: J Neuroimmunol. 1997 Jun;76(1-2):39-49
references.pmid: 9184631
references.citation: J Clin Invest. 2002 May;109(9):1153-63
references.pmid: 11994404
references.citation: Proc Natl Acad Sci U S A. 1997 Jun 10;94(12):6232-7
references.pmid: 9177200
references.citation: Nat Genet. 2007 Jul;39(7):857-64
references.pmid: 17554260
references.citation: Eur J Endocrinol. 2004 May;150(5):605-18
references.pmid: 15132715
references.citation: Am J Physiol Gastrointest Liver Physiol. 2001 May;280(5):G1022-9
references.pmid: 11292612
references.citation: J Biol Chem. 1999 Mar 5;274(10):6711-7
references.pmid: 10037769
references.citation: J Biol Chem. 2002 Mar 15;277(11):8955-60
references.pmid: 11779860
references.citation: J Immunol. 1986 Jun 1;136(11):3994-9
references.pmid: 3517163
references.citation: Science. 1996 Jul 5;273(5271):70-4
references.pmid: 8658199
references.citation: Endocrinology. 1993 Nov;133(5):2334-43
references.pmid: 8404686
references.citation: Br J Dermatol. 1988 Nov;119(5):639-42
references.pmid: 3207616
references.citation: J Clin Invest. 2008 Mar;118(3):1085-98
references.pmid: 18292808
references.citation: J Clin Invest. 1977 Feb;59(2):338-44
references.pmid: 299859
references.citation: Mol Cell Biol. 1999 May;19(5):3816-28
references.pmid: 10207105
references.citation: N Engl J Med. 2000 Jun 1;342(22):1633-7
references.pmid: 10833209
references.citation: Proc Natl Acad Sci U S A. 1993 Nov 15;90(22):10553-7
references.pmid: 7504269
references.citation: Endocr Rev. 1998 Oct;19(5):625-46
references.pmid: 9793761
references.citation: Diabetologia. 2007 Jul;50(7):1463-71
references.pmid: 17476475
references.citation: Eur J Immunol. 1995 Apr;25(4):931-5
references.pmid: 7737296
references.citation: Proc Natl Acad Sci U S A. 1995 Jun 20;92(13):6190-4
references.pmid: 7541143
references.citation: Clin Exp Immunol. 2005 Mar;139(3):526-33
references.pmid: 15730399
references.citation: Endocrinology. 1988 Apr;122(4):1291-6
references.pmid: 3345714
references.citation: J Biol Chem. 1998 Jan 9;273(2):1144-9
references.pmid: 9422780
references.citation: Int J Cancer. 2003 Dec 20;107(6):873-7
references.pmid: 14601044
references.citation: Clin Endocrinol (Oxf). 2008 Dec;69(6):894-900
references.pmid: 18410545
references.citation: J Immunol. 2000 Apr 1;164(7):3806-14
references.pmid: 10725741
references.citation: Diabetologia. 2008 May;51(5):811-5
references.pmid: 18317720
references.citation: Endocrinology. 1995 Mar;136(3):1153-60
references.pmid: 7532579