title: Suppressors of cytokine signaling in health and disease.
abstract: Cytokines consist of a large family of secreted proteins, including pro-inflammatory agents, growth hormone and erythropoietin, that utilize the Janus kinase (JAK) signal transducer and activator of transcription (STAT) signal transduction pathway to mediate many of their key physiologic and pathologic actions. These actions include cytokine-mediated inflammation, immunoregulation, hematopoiesis and growth. The JAK-STAT pathway is regulated by several processes, among which negative feedback regulation by the suppressors of cytokine signaling (SOCS), members of a family of eight proteins, is particularly important. Each cytokine induces one or more specific SOCS proteins that in turn down-regulate the signal initiated by the cytokine. Through their impact on the cytokine-activated JAK-STAT pathway, the SOCS proteins are involved in many diseases that come to the attention of the pediatric nephrologist. For example, an increase in the expression of SOCS-2 and -3 may be a cause of growth hormone resistance and thus may contribute to the growth retardation that affects children with chronic renal failure. Because of their obvious biologic importance, the SOCS proteins have been the subject of intense research that includes the development of strategies to utilize these proteins to control cytokine-induced JAK/STAT signal transduction for therapeutic purposes.
authors.affiliation: Division of Nephrology Department of Medicine, Stanford University, Palo Alto, CA 94305, USA.
authors.forename: Jane C
authors.initials: JC
authors.lastname: Tan
authors.forename: Ralph
authors.initials: R
authors.lastname: Rabkin
mesh_terms: D000818:Animals; D002648:Child; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology*; D007674:Kidney Diseases / Q000503:physiopathology*; D012097:Repressor Proteins / Q000502:physiology*; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D014157:Transcription Factors / Q000502:physiology*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D012097:Repressor Proteins; C108944:SOCS1 protein, human; C106644:SOCS3 protein, human; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D014157:Transcription Factors
references.citation: Proc Natl Acad Sci U S A. 1998 Jan 6;95(1):114-9
references.pmid: 9419338
references.citation: Nature. 1994 Jul 14;370(6485):151-3
references.pmid: 8022485
references.citation: Proc Natl Acad Sci U S A. 2003 Feb 4;100(3):1016-21
references.pmid: 12552091
references.citation: J Am Soc Nephrol. 2004 Oct;15(10):2630-6
references.pmid: 15466267
references.citation: Oncogene. 2001 May 3;20(20):2499-513
references.pmid: 11420660
references.citation: Kidney Int Suppl. 1997 Mar;58:S106-13
references.pmid: 9067957
references.citation: Leuk Lymphoma. 2000 Jun;38(1-2):49-58
references.pmid: 10811447
references.citation: EMBO J. 1995 Jun 15;14(12):2816-26
references.pmid: 7796808
references.citation: J Clin Invest. 2001 Dec;108(12 ):1781-8
references.pmid: 11748261
references.citation: J Immunol. 2002 Apr 1;168(7):3181-7
references.pmid: 11907070
references.citation: J Immunol. 2004 Feb 15;172(4):2307-15
references.pmid: 14764699
references.citation: Oncogene. 2000 May 15;19(21):2511-22
references.pmid: 10851050
references.citation: Cell. 1999 Sep 3;98 (5):617-27
references.pmid: 10490101
references.citation: Diabetes. 2002 Jul;51(7):2270-81
references.pmid: 12086960
references.citation: Nat Genet. 2001 May;28(1):29-35
references.pmid: 11326271
references.citation: Growth Horm IGF Res. 2004 Jun;14 (3):200-6
references.pmid: 15125881
references.citation: J Cell Physiol. 2003 Nov;197(2):157-68
references.pmid: 14502555
references.citation: Nature. 1997 Jun 26;387(6636):921-4
references.pmid: 9202126
references.citation: Mol Cell Endocrinol. 2001 Oct 25;183(1-2):49-54
references.pmid: 11604224
references.citation: J Pediatr Endocrinol Metab. 2002 Jun;15(6):771-86
references.pmid: 12099386
references.citation: Nature. 1997 Jun 26;387(6636):917-21
references.pmid: 9202125
references.citation: FEBS Lett. 1999 Jun 18;453(1-2):63-6
references.pmid: 10403376
references.citation: Blood. 2003 Apr 1;101(7):2784-8
references.pmid: 12456503
references.citation: J Biol Chem. 2003 Jun 20;278(25):22696-702
references.pmid: 12682066
references.citation: J Biol Chem. 2002 Oct 25;277(43):40181-4
references.pmid: 12208853
references.citation: Cell. 1999 Sep 3;98 (5):609-16
references.pmid: 10490100
references.citation: Blood. 2002 Oct 15;100(8):2926-31
references.pmid: 12351404
references.citation: Nature. 1997 Jun 26;387(6636):924-9
references.pmid: 9202127
references.citation: Kidney Int. 2003 Sep;64(3):1141-51
references.pmid: 12911573
references.citation: Gynecol Oncol. 2000 Oct;79(1):67-73
references.pmid: 11006034
references.citation: Immunity. 2001 May;14 (5):535-45
references.pmid: 11371356
references.citation: J Biol Chem. 2004 Jan 9;279(2):821-4
references.pmid: 14607831
references.citation: J Clin Invest. 2002 May;109(9):1139-42
references.pmid: 11994401
references.citation: Proc Natl Acad Sci U S A. 2002 Jan 22;99(2):943-8
references.pmid: 11782537
references.citation: Mol Endocrinol. 2002 Jun;16(6):1394-406
references.pmid: 12040024
references.citation: J Mol Cell Cardiol. 2002 Nov;34(11):1443-53
references.pmid: 12431443
references.citation: J Biol Chem. 1998 Oct 23;273(43):28185-90
references.pmid: 9774439
references.citation: J Exp Med. 2002 Oct 7;196(7):979-90
references.pmid: 12370259
references.citation: Nat Immunol. 2003 Jun;4(6):551-6
references.pmid: 12754507
references.citation: Nat Med. 2003 Aug;9(8):1047-54
references.pmid: 12847520
references.citation: Nat Rev Mol Cell Biol. 2002 Sep;3(9):651-62
references.pmid: 12209125
references.citation: J Biol Chem. 1998 Sep 11;273(37):24095-101
references.pmid: 9727029
references.citation: Growth Horm IGF Res. 2004 Aug;14(4):270-6
references.pmid: 15231295
references.citation: Clin Cancer Res. 1999 Jun;5(6):1569-82
references.pmid: 10389946
references.citation: Cell. 1999 Aug 6;98(3):295-303
references.pmid: 10458605
references.citation: Gene. 2002 Feb 20;285(1-2):1-24
references.pmid: 12039028
references.citation: Arch Immunol Ther Exp (Warsz). 2004 Mar-Apr;52(2):69-82
references.pmid: 15179321
references.citation: Cell. 1996 Feb 9;84(3):443-50
references.pmid: 8608598
references.citation: J Clin Invest. 2003 Mar;111(6):915-24
references.pmid: 12639998
references.citation: J Immunol. 1999 Sep 1;163(5):2640-7
references.pmid: 10453004
references.citation: Immunity. 2003 Apr;18(4):475-87
references.pmid: 12705851
references.citation: Oncogene. 2000 May 15;19(21):2489-95
references.pmid: 10851047
references.citation: Recent Prog Horm Res. 2000;55:293-311
references.pmid: 11036942
references.citation: J Exp Med. 2001 Jan 15;193(2):263-9
references.pmid: 11208867
references.citation: J Immunol. 2001 Jun 15;166(12 ):7082-9
references.pmid: 11390452
references.citation: Oncogene. 2000 May 15;19(21):2645-56
references.pmid: 10851064
references.citation: Mol Cell Endocrinol. 2000 Feb 25;160(1-2):1-9
references.pmid: 10715533
references.citation: Mol Cell Biol. 1999 Sep;19(9):6396-407
references.pmid: 10454585
references.citation: J Immunol. 2002 Aug 1;169(3):1219-27
references.pmid: 12133942
references.citation: J Clin Invest. 2001 Aug;108(3):467-75
references.pmid: 11489940
references.citation: Proc Natl Acad Sci U S A. 2002 Oct 1;99(20):13003-8
references.pmid: 12242343
references.citation: Transplantation. 2003 Jun 15;75(11):1864-72
references.pmid: 12811247
references.citation: Trends Immunol. 2003 Dec;24(12):659-66
references.pmid: 14644140
references.citation: Mol Endocrinol. 2003 May;17(5):967-75
references.pmid: 12576487
references.citation: Oncogene. 2000 May 15;19(21):2474-88
references.pmid: 10851046
references.citation: J Exp Med. 2001 Feb 19;193(4):471-81
references.pmid: 11181699
references.citation: Endocrinology. 2003 Oct;144(10 ):4586-96
references.pmid: 12960061
references.citation: Cell. 1999 Sep 3;98 (5):597-608
references.pmid: 10490099
references.citation: Nature. 2000 Jun 29;405(6790):1069-73
references.pmid: 10890450
references.citation: J Biol Chem. 2002 Nov 15;277(46):43735-40
references.pmid: 12221108
references.citation: Nature. 1994 Jul 14;370(6485):153-7
references.pmid: 8022486
references.citation: J Biol Chem. 2003 May 9;278(19):16777-81
references.pmid: 12615922
references.citation: Nat Rev Drug Discov. 2004 Jul;3(7):555-64
references.pmid: 15232577
references.citation: J Am Soc Nephrol. 2004 Feb;15(2):276-85
references.pmid: 14747374
references.citation: Curr Opin Oncol. 1999 Nov;11(6):490-6
references.pmid: 10550013
references.citation: J Biol Chem. 2003 Jun 20;278(25):22755-61
references.pmid: 12665516
references.citation: Immunity. 2003 Sep;19(3):437-50
references.pmid: 14499118
references.citation: Am J Physiol Renal Physiol. 2004 Apr;286(4):F653-9
references.pmid: 14678947
references.citation: Nat Immunol. 2003 Jun;4(6):540-5
references.pmid: 12754505
references.citation: Oncogene. 2000 May 15;19(21):2496-504
references.pmid: 10851048