SOCS negative regulation of the JAK-STAT pathway

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Review Paper 01/06/2012
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SOCS negative regulation of the JAK-STAT pathway

Lawrence O. Flowers
Int. J. Biosci.2( 6), 13-23, June 2012.
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Abstract

The Janus kinase (JAK)-signal transducer and activator of transcription (STAT) canonical signal transduction pathway is activated primarily by cytokines, hormones, and growth factors and has been shown to play a role in many intracellular processes including cell differentiation, adaptive and innate immune responses, and cell growth. The JAK-STAT pathway has also been implicated to affect a wide variety of hematologic and non-hematologic diseases such as cancer and renal disease. JAK-STAT pathway activation is achieved through extracellular ligand binding resulting in transcription factor and receptor interactions and subsequent gene expression. Given the importance of the JAK-STAT pathway in human cellular functions, the regulation of this signal transduction pathway is vitally important. The current review focuses on the JAK-STAT pathway as well as the structure and function of the primary negative regulatory proteins of the JAK-STAT pathway, the suppressors of cytokine signaling (SOCS) proteins. SOCS proteins facilitate the negative regulation of signal transduction pathways by targeting specific signaling components for proteosomal destruction. Understanding the role of SOCS proteins in disease progression is of great importance to microbiologists and immunologists. Much research is directed at identifying and developing specific JAK-STAT inhibitors and SOCS inhibitors that may prove useful in counteracting the cellular effects observed in many carcinomas and infectious diseases.

VIEWS 7

Alexander, WS. 2002. Suppressors of cytokine signalling (SOCS) in the immune system. Nat. Rev. Immunol. 2, 410-416.

Akhtar LN, Benveniste EN. 2011. Viral exploitation of host SOCS protein functions. J. Virol. 85, 1912-1921.

Alexander WS, Starr R, Fenner JE, Scott CL, Handman E, Sprigg NS, Corbin JE, Cornish AL, Darwiche R, Owczarek CM, Kay TW, Nicola NA, Hertzog PJ, Metcalf D, Hilton DJ. 1999. SOCS1 is a critical inhibitor of interferon gamma signaling and prevents the potentially fatal neonatal actions of this cytokine. Cell 98, 597-608.

Aringer M, Cheng A, Nelson JW, Chen M, Sudarshan C, Zhou YJ, O’Shea JJ. 1999. Janus kinases and their role in growth and disease. Life Sci. 64, 2173-2186.

Chuang PY, He JC. 2010. JAK/STAT signaling in renal diseases. Kidney Int. 78, 231-234.

Emanuelli B, Peraldi P, Filloux C, Sawka-Verhelle D, Hilton D, Van Obberghen E. 2000. SOCS-3 is an insulin-induced negative regulator of insulin signaling. J. Biol. Chem. 275, 15985-15991.

Feng J, Witthuhn BA, Matsuda T, Kohlhuber F, Kerr IM, Ihle JN. 1997. Activation of Jak2 catalytic activity requires phosphorylation of Y1007 in the kinase activation loop. Mol. Cell. Biol. 17, 2497-2501.

Frantsve J, Schwaller J, Sternberg DW, Kutok J, Gilliland DG. 2001. Socs-1 inhibits TEL-JAK2-mediated transformation of hematopoietic cells through inhibition of JAK2 kinase activity and induction of proteasome-mediated degradation. Mol. Cell. Biol. 21, 3547-3557.

Fujimoto M, Naka T. 2003. Regulation of cytokine signaling by SOCS family molecules. Trends Immunol. 24, 659-666.

Hilton DJ, Richardson RT, Alexander WS, Viney EM, Willson TA, Sprigg NS, Starr R, Nicholson SE, Metcalf D, Nicola NA. 1998. Twenty proteins containing a C-terminal SOCS box form five structural classes. Proc. Acad. Nat. Sci. 95, 114-119.

Ho JM, Nguyen MH, Dierov JK, Badger KM, Beattie BK, Tartaro P, Haq R, Zanke BW, Carroll MP, Barber DL. 2002. TEL-JAK2 constitutively activates the extracellular signal-regulated kinase (ERK), stress-activated protein/Jun kinase (SAPK/JNK), and p38 signaling pathways. Blood 100, 1438-1448.

Horvath CM. 2000. STAT proteins and transcriptional responses to extracellular signals. Trends Biochem. Sci. 25, 496-502.

Ishihara K, Hirano T. 2002. Molecular basis of the cell specificity of cytokine action. Biochim. Biophys. Acta. 1592, 281-296.

Johnson HM, Bazer FW, Szente BE, Jarpe, MA. 1994. How interferons fight disease. Sci. Am. 270, 68-75.

Karaghiosoff M, Neubauer H, Lassnig C, Kovarik P, Schindler H, Pircher H, McCoy B, Bogdan C, Decker T, Brem G, Pfeffer K, Müller M. 2000. Partial impairment of cytokine responses in Tyk2-deficient mice. Immunity 13, 549-560.

Kisseleva T, Bhattacharya S, Braunstein J, Schindler CW. 2002. Signaling through the JAK/STAT pathway, recent advances and future challenges. Gene 285, 1-24.

Kotenko SV, Pestka S. 2000. Jak-Stat signal transduction pathway through the eyes of cytokine class II receptor complexes. Oncogene 19, 2557-2565.

Kubo M, Hanada T, Yoshimura A. 2003. Suppressors of cytokine signaling and immunity. Nat. Immunol. 4, 1169-1176.

Lacronique, V., Boureux, A., Valle, V. D., Poirel, H., Quang, C. T., Mauchauffe, M., Berthou, C., Lessard, M., Berger, R., Ghysdael, J., and Bernard, O. A. Bernard. 1997. A TEL- JAK2 fusion protein with constitutive kinase activity in human leukemia. Science 278, 1309-1312.

Larsen L, Röpke C. 2002. Suppressors of cytokine signalling: SOCS. APMIS 110, 833-844.

Leonard W. 2001. Cytokines and Immunodeficiency Diseases. Nat. Rev. Immunol. 1, 200-208.

Leonard WJ, O’Shea JJ. 1998. Jaks and STATs: biological implications. Annu. Rev. Immunol. 16, 293-322.

Liongue C, O’Sullivan LA, Trengove MC, Ward AC. 2012. Evolution of JAK-STAT pathway components: mechanisms and role in immune system development. PLoS One 7, 1-16.

Liu X, He Z, Li CH, Huang G, Ding C, Liu H. 2012. Correlation analysis of JAK-STAT pathway components on prognosis of patients with prostate cancer. Pathol. Oncol. Res. 18, 17-23.

Lucas JA, Miller AT, Atherly LO, Berg LJ. 2003. The role of Tec family kinases in T cell development and function. Immunol. Rev. 191, 119-138.

Marrero MB, Banes-Berceli AK, Stern DM, Eaton DC. 2006. Role of the JAK/STAT signaling pathway in diabetic nephropathy. Am. J. Physiol. Renal Physiol. 290, F762-F768.

Monni R, Santos SC, Mauchauffe M, Berger R, Ghysdael J, Gouilleux F, Gisselbrecht S, Bernard O, Penard-Lacronique V. 2001. The TEL-Jak2 oncoprotein induces Socs1 expression and altered cytokine response in Ba/F3 cells. Oncogene 20, 849-858.

Ohya K, Kajigaya S, Yamashita Y, Miyazato A, Hatake K, Miura Y, Ikeda U, Shimada K, Ozawa K, Mano H. 1997. SOCS-1/JAB/SSI-1 can bind to and suppress Tec protein-tyrosine kinase. J. Biol. Chem. 272, 27178-27182.

Parganas E, Wang D, Stravopodis D, Topham DJ, Marine JC, Teglund S, Vanin EF, Bodner S, Colamonici OR, van Deursen JM, Grosveld G, Ihle JN. 1998. Jak2 is essential for signaling through a variety of cytokine receptors. Cell 93, 385-395.

Peeters P, Raynaud SD, Cools J, Wlodarska I, Grosgeorge J, Philip P, Monpoux F, Van Rompaey L, Baens M, Van den Berghe H, Marynen P. 1997. Fusion of TEL, the ETS-variant gene 6 (ETV6), to the receptor-associated kinase JAK2 as a result of t(9;12) in a lymphoid and t(9;15;12) in a myeloid leukemia. Blood 90, 2535-2540.

Sakamoto H, Yasukawa H, Masuhara M, Tanimura S, Sasaki A, Yuge K, Ohtsubo M, Ohtsuka A, Fujita T, Ohta T, Furukawa Y, Iwase S, Yamada H, Yoshimura A. 1998. A Janus kinase inhibitor, JAB, is an interferon-gamma-inducible gene and confers resistance to interferons. Blood 92, 1668-1676.

Samuel CE. 2001. Antiviral actions of interferons. Clin. Microbiol. Rev. 14, 778-809.

Stark GR, Darnell JE. 2012. The JAK-STAT Pathway at Twenty. Immunity 36, 503-514.

Ramgolam VS, Markovic-Plese S. 2011. Regulation of suppressors of cytokine signaling as a therapeutic approach in autoimmune diseases, with an emphasis on multiple sclerosis. J. Signal Transduct. 2011, 1-7.

Roberts AW, Robb L, Rakar S, Hartley L, Cluse L, Nicola NA, Metcalf D, Hilton DJ, Alexander WS. 2001. Placental defects and embryonic lethality in mice lacking suppressor of cytokine signaling 3. Proc. Acad. Nat. Sci. 98, 9324-9329.

Taniguchi T. 1995. Cytokine signaling through nonreceptor protein tyrosine kinases. Science 268, 251-255.

Verma A, Kambhampati S, Parmar S, Platanias LC. 2003. Jak family of kinases in cancer. Cancer Metastasis Rev. 22, 423-434.

Yasukawa H, Misawa H, Sakamoto H, Masuhara M, Sasaki A, Wakioka T, Ohtsuka S, Imaizumi T, Matsuda T, Ihle JN, Yoshimura A. 1999. The JAK-binding protein JAB inhibits Janus tyrosine kinase activity through binding in the activation loop. Embo J. 18, 1309-1320.

You Z, Xu D, Ji J, Guo W, Zhu W, He J. 2012. JAK/STAT signal pathway activation promotes progression and survival of human oesophageal squamous cell carcinoma. Clin. Transl. Oncol. 14, 143-149.

Zhang J, Li H, Yu JP, Wang SE, Ren XB. 2012. Role of SOCS1 in tumor progression and therapeutic application. Int. J. Cancer. 30, 1971-1980.