Suppressors of cytokine signaling in health and disease.
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.
Tan
Jane C
JC
Division of Nephrology Department of Medicine, Stanford University, Palo Alto, CA 94305, USA.
Rabkin
Ralph
R
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*
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
Proc Natl Acad Sci U S A. 1998 Jan 6;95(1):114-9
9419338
Nature. 1994 Jul 14;370(6485):151-3
8022485
Proc Natl Acad Sci U S A. 2003 Feb 4;100(3):1016-21
12552091
J Am Soc Nephrol. 2004 Oct;15(10):2630-6
15466267
Oncogene. 2001 May 3;20(20):2499-513
11420660
Kidney Int Suppl. 1997 Mar;58:S106-13
9067957
Leuk Lymphoma. 2000 Jun;38(1-2):49-58
10811447
EMBO J. 1995 Jun 15;14(12):2816-26
7796808
J Clin Invest. 2001 Dec;108(12 ):1781-8
11748261
J Immunol. 2002 Apr 1;168(7):3181-7
11907070
J Immunol. 2004 Feb 15;172(4):2307-15
14764699
Oncogene. 2000 May 15;19(21):2511-22
10851050
Cell. 1999 Sep 3;98 (5):617-27
10490101
Diabetes. 2002 Jul;51(7):2270-81
12086960
Nat Genet. 2001 May;28(1):29-35
11326271
Growth Horm IGF Res. 2004 Jun;14 (3):200-6
15125881
J Cell Physiol. 2003 Nov;197(2):157-68
14502555
Nature. 1997 Jun 26;387(6636):921-4
9202126
Mol Cell Endocrinol. 2001 Oct 25;183(1-2):49-54
11604224
J Pediatr Endocrinol Metab. 2002 Jun;15(6):771-86
12099386
Nature. 1997 Jun 26;387(6636):917-21
9202125
FEBS Lett. 1999 Jun 18;453(1-2):63-6
10403376
Blood. 2003 Apr 1;101(7):2784-8
12456503
J Biol Chem. 2003 Jun 20;278(25):22696-702
12682066
J Biol Chem. 2002 Oct 25;277(43):40181-4
12208853
Cell. 1999 Sep 3;98 (5):609-16
10490100
Blood. 2002 Oct 15;100(8):2926-31
12351404
Nature. 1997 Jun 26;387(6636):924-9
9202127
Kidney Int. 2003 Sep;64(3):1141-51
12911573
Gynecol Oncol. 2000 Oct;79(1):67-73
11006034
Immunity. 2001 May;14 (5):535-45
11371356
J Biol Chem. 2004 Jan 9;279(2):821-4
14607831
J Clin Invest. 2002 May;109(9):1139-42
11994401
Proc Natl Acad Sci U S A. 2002 Jan 22;99(2):943-8
11782537
Mol Endocrinol. 2002 Jun;16(6):1394-406
12040024
J Mol Cell Cardiol. 2002 Nov;34(11):1443-53
12431443
J Biol Chem. 1998 Oct 23;273(43):28185-90
9774439
J Exp Med. 2002 Oct 7;196(7):979-90
12370259
Nat Immunol. 2003 Jun;4(6):551-6
12754507
Nat Med. 2003 Aug;9(8):1047-54
12847520
Nat Rev Mol Cell Biol. 2002 Sep;3(9):651-62
12209125
J Biol Chem. 1998 Sep 11;273(37):24095-101
9727029
Growth Horm IGF Res. 2004 Aug;14(4):270-6
15231295
Clin Cancer Res. 1999 Jun;5(6):1569-82
10389946
Cell. 1999 Aug 6;98(3):295-303
10458605
Gene. 2002 Feb 20;285(1-2):1-24
12039028
Arch Immunol Ther Exp (Warsz). 2004 Mar-Apr;52(2):69-82
15179321
Cell. 1996 Feb 9;84(3):443-50
8608598
J Clin Invest. 2003 Mar;111(6):915-24
12639998
J Immunol. 1999 Sep 1;163(5):2640-7
10453004
Immunity. 2003 Apr;18(4):475-87
12705851
Oncogene. 2000 May 15;19(21):2489-95
10851047
Recent Prog Horm Res. 2000;55:293-311
11036942
J Exp Med. 2001 Jan 15;193(2):263-9
11208867
J Immunol. 2001 Jun 15;166(12 ):7082-9
11390452
Oncogene. 2000 May 15;19(21):2645-56
10851064
Mol Cell Endocrinol. 2000 Feb 25;160(1-2):1-9
10715533
Mol Cell Biol. 1999 Sep;19(9):6396-407
10454585
J Immunol. 2002 Aug 1;169(3):1219-27
12133942
J Clin Invest. 2001 Aug;108(3):467-75
11489940
Proc Natl Acad Sci U S A. 2002 Oct 1;99(20):13003-8
12242343
Transplantation. 2003 Jun 15;75(11):1864-72
12811247
Trends Immunol. 2003 Dec;24(12):659-66
14644140
Mol Endocrinol. 2003 May;17(5):967-75
12576487
Oncogene. 2000 May 15;19(21):2474-88
10851046
J Exp Med. 2001 Feb 19;193(4):471-81
11181699
Endocrinology. 2003 Oct;144(10 ):4586-96
12960061
Cell. 1999 Sep 3;98 (5):597-608
10490099
Nature. 2000 Jun 29;405(6790):1069-73
10890450
J Biol Chem. 2002 Nov 15;277(46):43735-40
12221108
Nature. 1994 Jul 14;370(6485):153-7
8022486
J Biol Chem. 2003 May 9;278(19):16777-81
12615922
Nat Rev Drug Discov. 2004 Jul;3(7):555-64
15232577
J Am Soc Nephrol. 2004 Feb;15(2):276-85
14747374
Curr Opin Oncol. 1999 Nov;11(6):490-6
10550013
J Biol Chem. 2003 Jun 20;278(25):22755-61
12665516
Immunity. 2003 Sep;19(3):437-50
14499118
Am J Physiol Renal Physiol. 2004 Apr;286(4):F653-9
14678947
Nat Immunol. 2003 Jun;4(6):540-5
12754505
Oncogene. 2000 May 15;19(21):2496-504
10851048