Abstract
Recently, constitutive activation of JAK kinases (JAKs) and/or signal transducers and activators of transcription (STATs) has been reported in growing numbers of human cancer cells as well as oncogene-transformed cells. JAB/SOCS-1 has been shown to be an intrinsic JAK tyrosine kinase inhibitor and to suppress the cytokine-dependent JAK–STAT pathway. In this report, we investigated the effect of ectopic expression of JAB on v-Src-induced JAK–STAT activation. Forced expression of JAB in v-Src-transformed NIH3T3 cells neither suppressed phosphorylation of STAT3 and JAK1/JAK2 nor blocked STAT3-reporter gene activation. Colony forming assay also showed that JAB did not suppress v-Src-induced transformation of NIH3T3 cells, while dominant negative STAT3 suppressed it. In contrast, JAB could downregulate phosphorylation of STAT1 and STAT3 induced by interferon gamma (IFNγ) and interleukin-6 (IL-6) plus soluble IL6 receptor (sIL-6R), respectively. Furthermore, in vitro kinase assay indicated that JAB suppressed hyperactivation of JAK1/JAK2 and JAK1 induced by INFγ and IL-6 plus sIL-6R respectively, but not v-Src-induced basal JAK1/JAK2 activity. Nevertheless, both JAK1/JAK2 activated by v-Src and that activated by IL-6 plus sIL-6R could similarly bind JAB. These results clearly demonstrate that JAB distinguishes cytokine-induced JAK–STAT signaling from v-Src-induced one and can not suppress the transformation with v-Src.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
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 and Hilton DJ. . 1999 Cell 98: 597–608.
Bromberg JF, Horvath CM, Besser D, Lathem WW and Darnell JEJ. . 1998 Mol. Cell. Biol. 18: 2553–2558.
Bromberg JF, Wrzeszczynska MH, Devgan G, Zhao Y, Pestell RG, Albanese C and Darnell JEJ. . 1999 Cell 98: 295–303.
Campbell GS, Yu CL, Jove R and Carter-Su C. . 1997 J. Biol. Chem. 272: 2591–2594.
Cao X, Tay A, Guy GR and Tan YH. . 1996 Mol. Cell. Biol. 16: 1595–1603.
Catlett-Falcone R, Landowski TH, Oshiro MM, Turkson J, Levitzki A, Savino R, Ciliberto G, Moscinski L, Fernandez-Luna JL, Nunez G, Dalton WS and Jove R. . 1999 Immunnity 10: 105–115.
Chaturvedi P, Reddy MV and Reddy EP. . 1998 Oncogene 16: 1749–1758.
Dainal NN, Pernis A and Rothman PB. . 1995 Science 269: 1875–1877.
Darnell JEJ, Kerr IM and Stark GR. . 1994 Science 264: 1415–1421.
Endo TA, Masuhara M, Yokouchi M, Suzuki R, Sakamoto H, Mitsui K, Matsumoto A, Tanimura S, Ohtsubo M, Misawa H, Miyazaki T, Leonor N, Taniguchi T, Fujita T, Kanakura Y, Komiya S and Yoshimura A. . 1997 Nature 387: 921–924.
Gracia R, Yu CL, Hudnall A, Catlett R, Nelson KL, Smithgall T, Fujita DJ, Ethier SP and Jove R. . 1997 Cell Growth. Differ. 8: 1267–1276.
Gracia R and Jove R. . 1998 J. Biomed. Sci. 5: 79–85.
Grandis JR, Drenning SD, Chakraborty A, Zhou MY, Zeng Q, Pitt AS and Tweardy DJ. . 1998 J. Clin. Invest 102: 385–392.
Hamaguchi M, Xiao H, Uehara Y, Ohnishi Y and Nagai Y. . 1993 Oncogene 8: 559–564.
Ihle JN. . 1995 Nature 377: 591–594.
Ihle JN. . 1996 Cell 84: 331–334.
Marine JC, Topham DJ, McKay C, Wang D, Parganas E, Stravopodis D, Yoshimura A and Ihle JN. . 1999 Cell 98: 609–616.
Masuhara M, Sakamoto H, Matsumoto A, Suzuki R, Yasukawa H, Mitsui K, Wakioka T, Tanimura S, Sasaki A, Misawa H, Yokouchi M, Ohtsubo M and Yoshimura A. . 1997 Biochem Biophys Res Commun. 239: 439–446.
Migone TS, Lin JX, Cereseto A, Mulloy JC, O'Shea JJ, Franchini G and Leonard WJ. . 1995 Science 269: 79–81.
Naka T, Narazaki M, Hirata M, Matsumoto T, Minamoto S, Aono A, Nishimoto N, Kajita T, Taga T, Yoshizaki K, Akira S and Kishimoto T. . 1997 Nature 387: 924–929.
Nakajima K, Yamanaka Y, Nakae K, Kojima H, Ichiba M, Kiuchi N, Kitaoka T, Fukada T, Hibi M and Hirano T. . 1996 EMBO J. 15: 3651–3658.
Nicholson SE, Willson TA, Farley A, Starr R, Zhang JG, Baca M, Alexander WS, Metcalf D, Hilton DJ and Nicola NA. . 1999 EMBO J. 18: 375–385.
Niu G, Heller R, Catlett-Falcone R, Coppola D, Jaroszeski M, Dalton W, Jove R and Yu H. . 1999 Cancer Res. 15: 5059–5063.
O'Shea JJ. . 1997 Immunity 7: 1–11.
Parganas E, Wang D, Stravopodis D, Topham DJ, Marine JC, Teglund S, Vanin EF, Bodner S, Colamonici OR, van Deursen JM, Grosveld G and Ihle JN. . 1998 Cell 93: 385–395.
Rodig SJ, Meraz MA, White JM, Lampe PA, Riley JK, Arthur CD, King KL, Sheehan KCF, Yin L, Pennica D, Johnson EMJ and Shreiber RD. . 1998 Cell 93: 373–383.
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 and Yoshimura A. . 1998 Blood 92: 1668–1676.
Starr R, Willson TA, Viney EM, Murray LJ, Rayner JR, Jenkins BJ, Gonda TJ, Alexander WS, Metcalf D, Nicola NA and Hilton DJ. . 1997 Nature 387: 917–921.
Turkson J, Bowman T, Garcia R, Caldenhoven E, Groot RPD and Jove R. . 1998 Mol. Cell. Biol. 18: 2545–2552.
Yasukawa H, Misawa H, Sakamoto H, Masuhara M, Sasaki A, Wakioka T, Ohtsuka S, Imaizumi T, Matsuda T, Ihle JN and Yoshimura A. . 1999 EMBO J. 18: 1309–1320.
Yu CL, Meyer DJ, Campbell GS, Larner AC, Carter-Su C, Schwartz J and Jove R. . 1995 Science 269: 81–83.
Acknowledgements
We thank Dr Toshio Hirano for STAT3 plasmid and Dr Izumi Nakashima for critical reading of the manuscript. IL-6 is a gift from Kirin Brewer Co. Ltd. This work was supported by grant-in-aids for COE Research from the Ministry of Education, Science and Culture of Japan and for Scientific Research of Japan Society for Promotion of Science.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Iwamoto, T., Senga, T., Naito, Y. et al. The JAK-inhibitor, JAB/SOCS-1 selectively inhibits cytokine-induced, but not v-Src induced JAK–STAT activation. Oncogene 19, 4795–4801 (2000). https://doi.org/10.1038/sj.onc.1203829
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1203829
Keywords
This article is cited by
-
Constitutive SOCS-3 expression protects T-cell lymphoma against growth inhibition by IFNα
Leukemia (2005)
-
Arsenic inhibition of the JAK-STAT pathway
Oncogene (2004)
-
JAKs, STATs and Src kinases in hematopoiesis
Oncogene (2002)