The DOI matches its Crossref record; 36 of the 36 references it cites were found in a registry or an index.
SOCS3 Exerts Its Inhibitory Function on Interleukin-6 Signal Transduction through the SHP2 Recruitment Site of gp130
Open accessAbstract
Interleukin-6 is involved in the regulation of many biological activities such as gene expression, cell proliferation, and differentiation. The control of the termination of cytokine signaling is as important as the regulation of initiation of signal transduction pathways. Three families of proteins involved in the down-regulation of cytokine signaling have been described recently: (i) SH2 domain-containing protein-tyrosine phosphatases (SHP), (ii) suppressors of cytokine signaling (SOCS), and (iii) protein inhibitors of activated STATs (PIAS). We have analyzed the interplay of two inhibitors in the signal transduction pathway of interleukin-6 and demonstrate that the tyrosine phosphatase SHP2 and SOCS3 do not act independently but are functionally linked. The activation of one inhibitor modulates the activity of the other; Inhibition of SHP2 activation leads to increased SOCS3-mRNA levels, whereas increased expression of SOCS3 results in a reduction of SHP2 phosphorylation after activation of the interleukin-6 signal transduction pathway. Furthermore, we show that tyrosine 759 in gp130 is essential for both SHP2 and SOCS3 but not for SOCS1 to exert their inhibitory activities on interleukin-6 signal transduction. Besides SHP2, SOCS3 also interacts with the Tyr(P)-759 peptide of gp130. Taken together, our results suggest differences in the function of SOCS1 and SOCS3 and a link between SHP2 and SOCS3.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Inhibition of SOCS3 expression [37] or lack of SOCS3 binding sites in gp130 results in sustained STAT3 activation and altered physiological outcomes in response to IL-6 [38].”
From The tyrosine phosphatase SHP2 increases robustness and information transfer within IL-6-induced JAK/STAT signalling (2021) · cites this paper as [38]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“In the first mechanism, nascent SOCS-3 blocks the activation of STAT-3 by binding to the receptor complex via gp130 at tyrosine 759 (34,35) and/or by binding and inhibiting Jak2 activity (36).”
From Expression of suppressors of cytokine signaling during liver regeneration (2001) · cites this paper as [34]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Molecular cloning: A laboratory manual
Deininger, P. L. (1990) · Analytical Biochemistry · doi:10.1016/0003-2697(90)90595-z · Cited by 84,684
Interleukin-6-type cytokine signalling through the gp130/Jak/STAT pathway
HEINRICH, P. C., BEHRMANN, I., MÜLLER-NEWEN, G., SCHAPER, F., & GRAEVE, L. (1998) · Biochemical Journal · doi:10.1042/bj3340297 · Cited by 2,130
Self-citationZhong, Z., Wen, Z., & Darnell, J. E. (1994) · Science · doi:10.1126/science.8140422 · Cited by 2,070
A family of cytokine-inducible inhibitors of signalling
Starr, R., Willson, T. A., Viney, E. M., Murray, L. J. L., Rayner, J. R., Jenkins, B. J., Gonda, T. J., Alexander, W. S., Metcalf, D., Nicola, N. A., et al. (1997) · Nature · doi:10.1038/43206 · Cited by 2,066
A new protein containing an SH2 domain that inhibits JAK kinases
Endo, T. A., Masuhara, M., Yokouchi, M., Suzuki, R., Sakamoto, H., Mitsui, K., Matsumoto, A., Tanimura, S., Ohtsubo, M., Misawa, H., et al. (1997) · Nature · doi:10.1038/43213 · Cited by 1,408
Structure and function of a new STAT-induced STAT inhibitor
Naka, T., Narazaki, M., Hirata, M., Matsumoto, T., Minamoto, S., Aono, A., Nishimoto, N., Kajita, T., Taga, T., Yoshizaki, K., et al. (1997) · Nature · doi:10.1038/43219 · Cited by 1,040
Specific Inhibition of Stat3 Signal Transduction by PIAS3
Chung, C. D., Liao, J., Liu, B., Rao, X., Jay, P., Berta, P., & Shuai, K. (1997) · Science · doi:10.1126/science.278.5344.1803 · Cited by 980
Stahl, N., Farruggella, T. J., Boulton, T. G., Zhong, Z., Darnell, J. E., & Yancopoulos, G. D. (1995) · Science · doi:10.1126/science.7871433 · Cited by 979
Association and Activation of Jak-Tyk Kinases by CNTF-LIF-OSM-IL-6 β Receptor Components
Stahl, N., Boulton, T. G., Farruggella, T., Ip, N. Y., Davis, S., Witthuhn, B. A., Quelle, F. W., Silvennoinen, O., Barbieri, G., Pellegrini, S., et al. (1994) · Science · doi:10.1126/science.8272873 · Cited by 979
Lütticken, C., Wegenka, U. M., Yuan, J., Buschmann, J., Schindler, C., Ziemiecki, A., Harpur, A. G., Wilks, A. F., Yasukawa, K., Taga, T., et al. (1994) · Science · doi:10.1126/science.8272872 · Cited by 814
Self-citation
Flagged first, then by citations
Research works printed but not linked: 2
- Wegenka, 1993, Mol. Cell. Biol., 13, 276
- Yuan, 1994, Mol. Cell. Biol., 14, 1657
Cited by
Sorted by citations
Items 201–300 of 388
Jenkins, B. J., Grail, D., Inglese, M., Quilici, C., Bozinovski, S., Wong, P., & Ernst, M. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.4.1453-1463.2004 · Cited by 43
“Conversely, the gp130 substitution mutation removes the phosphotyrosine residue that simultaneously provides a binding site for SHP2 and SOCS3, and therefore disrupts the capacity of SOCS3 to negatively regulate gp130-dependent signaling (35) and of SHP2 to dephosphorylate critical tyrosine residues in the gp130-JAK s…”
BackgroundHanada, T., Kinjyo, I., Inagaki-Ohara, K., & Yoshimura, A. (2003) · Springer eBooks · doi:10.1007/s10254-003-0015-z · Cited by 43
Overexpression of SOCS3 inhibits astrogliogenesis and promotes maintenance of neural stem cells
Cao, F., Hata, R., Zhu, P., Ma, Y., Tanaka, J., Hanakawa, Y., Hashimoto, K., Niinobe, M., Yoshikawa, K., & Sakanaka, M. (2006) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2006.03890.x · Cited by 42
“SOCS3 has been shown to interact with gp130 and Jak, and this interaction results in relatively specific inhibition of gp130 signaling (Nicholson et al. 2000; Schmitz et al. 2000).”
BackgroundIdentification of a nuclear localization signal in suppressor of cytokine signaling 1
Baetz, A., Koelsche, C., Strebovsky, J., Heeg, K. M., & Dalpke, A. H. (2008) · The FASEB Journal · doi:10.1096/fj.08-116079 · Cited by 42
“All 8 proteins (SOCS1 to SOCS7, CIS) belonging to the SOCS family are composed of a central src-homology 2 (SH2) region that mediates binding to tyrosine-phosphorylated residues within cytokine receptor chains or JAKs themselves (1, 2).”
BackgroundFriederichs, K., Schmitz, J., Weißenbach, M., Heinrich, P. C., & Schaper, F. (2001) · European Journal of Biochemistry · doi:10.1046/j.0014-2956.2001.02586.x · Cited by 43
Self-citationPark, K. W., Lin, C., & Lee, Y. (2014) · Experimental Neurology · doi:10.1016/j.expneurol.2014.06.013 · Cited by 43
“SOCS3 binds to gp130, a common signal transducing subunit with interleukin-6 (IL-6), or to Janus kinase1 (JAK1) and JAK2, to inhibit signal transduction (Nicholson et al., 2000; Schmitz et al., 2000).”
BackgroundMolecular and cellular features of hepatic regeneration
Black, D., Lyman, S., Heider, T. R., & Behrns, K. E. (2004) · Journal of Surgical Research · doi:10.1016/j.jss.2003.10.026 · Cited by 42
Calegari, V. C., Bezerra, R. M. N., Torsoni, M. A., Torsoni, A. S., Franchini, K. G., Saad, M. J. A., & Velloso, L. A. (2003) · Endocrinology · doi:10.1210/en.2003-0046 · Cited by 42
“The translated SOCS3 then migrates and interacts with Tyr(759) in the IL-6 receptor subunit gp130, thereby inhibiting further activation of the IL6/JAK2/STAT signaling pathway (17).”
BackgroundComparative proteomics analysis of human pituitary adenomas: Current status and future perspectives
Zhan, X., & Desiderio, D. M. (2004) · Mass Spectrometry Reviews · doi:10.1002/mas.20039 · Cited by 41
“Some studies found that SOCS-3 played a role in integrating the neuro–immuno– endocrine interface (Auernhammer & Melmed, 2001), inhibited IL-6 signaling transduction (Schmitz et al., 2000), and regulated in the pituitary the POMC production that is induced by LIF (Bousquet, Susini, & Melmed, 1999).”
BackgroundStroß, C., Radtke, S., Clahsen, T., Gerlach, C., Volkmer, R., Schaper, F., Heinrich, P. C., & Hermanns, H. M. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m511212200 · Cited by 41
Self-citationActivating mutations of the gp130/JAK/STAT pathway in human diseases
Lokau, J., & Garbers, C. (2018) · Advances in protein chemistry and structural biology · doi:10.1016/bs.apcsb.2018.11.007 · Cited by 41
Mechanisms of SOCS3 Phosphorylation upon Interleukin-6 Stimulation
Sommer, U., Schmid, C., Sobota, R. M., Lehmann, U., Stevenson, N. J., Johnston, J. A., Schaper, F., Heinrich, P. C., & Haan, S. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m506008200 · Cited by 42
Self-citationShp2 as a therapeutic target for leptin resistance and obesity
Feng, G. (2006) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.10.1.135 · Cited by 39
“Interestingly, like Tyr985 on LepRb, this Shp2-binding site has subsequently been shown to recruit Socs3 as well [45].”
Backgroundde Rezende, L. F., Vieira, A. S., Negro, A., Langone, F., & Boschero, A. C. (2009) · Cytokine · doi:10.1016/j.cyto.2008.12.014 · Cited by 38
Targeting Systemic Sclerosis from Pathogenic Mechanisms to Clinical Manifestations: Why IL-6?
Cardoneanu, A., Burlui, A., Macovei, L. A., Bratoiu, I., Richter, P., & Rezuş, E. (2022) · Biomedicines · doi:10.3390/biomedicines10020318 · Cited by 39
Shen, A., Chen, Y., Hong, F., Lin, J., Wei, L., Hong, Z., Sferra, T. J., & Peng, J. (2012) · Oncology Reports · doi:10.3892/or.2012.2067 · Cited by 38
“5B, IL-6 stimulation induced SOCS3 expression, which is consistent with previous studies (39,40).”
Ahmed, S. T., Mayer, A., Ji, J.-D., & Ivashkiv, L. B. (2002) · Journal of Leukocyte Biology · doi:10.1189/jlb.72.1.154 · Cited by 38
Interleukin 11 (IL-11): Role(s) in Breast Cancer Bone Metastases
Maroni, P., Bendinelli, P., Ferraretto, A., & Lombardi, G. (2021) · Biomedicines · doi:10.3390/biomedicines9060659 · Cited by 39
“Upon activation, gp130 offers also a binding site (Y759) for the Src Biomedicines 2021, 9, 659 4 of 15 homology-2 domain-containing phosphatase (SHP2) [43].”
BackgroundInfluentialJAK-STAT signaling pathway in non-infectious uveitis
Su, Y., Tao, T., Liu, X., & Su, W. (2022) · Biochemical Pharmacology · doi:10.1016/j.bcp.2022.115236 · Cited by 38
Ciampone, S., Borges, R. D. C. P., de Lima, I. P., Mesquita, F. F., Cambiucci, E. C., & Gontijo, J. A. R. (2011) · Journal of the Renin-Angiotensin-Aldosterone System · doi:10.1177/1470320311408750 · Cited by 37
Matsushita, K., Itoh, S., Ikeda, S., Yamamoto, Y., Yamauchi, Y., & Hayashi, M. (2014) · Journal of Cellular Biochemistry · doi:10.1002/jcb.24777 · Cited by 37
“E-mail: ito@dent.osaka-u.ac.jp Manuscript Received: 14 November 2013; Manuscript Accepted: 22 January 2014 Accepted manuscript online in Wiley Online Library (wileyonlinelibrary.com): 25 January 2014 DOI 10.1002/jcb.24777 © 2014 Wiley Periodicals, Inc. 1262 by the JAK/STAT signaling pathway.”
BackgroundInfluentialSHP2 is required for BCR-ABL1-induced hematologic neoplasia
Gu, S. S., Sayad, A., Chan, G., Yang, W., Lu, Z., Virtanen, C., Etten, R. A. V., & Neel, B. G. (2017) · Leukemia · doi:10.1038/leu.2017.250 · Cited by 38
Park, K. W., Nozell, S. E., & Benveniste, E. N. (2012) · PLoS ONE · doi:10.1371/journal.pone.0050874 · Cited by 36
“SOCS3 binds phospho-tyrosine residue 759 within gp130, subsequently inhibiting signal transduction [17,18].”
BackgroundZhou, Y. Y., Tao, H., Wang, A., Zhong, Z., Wu, X., Wang, M., Bian, Z., Wang, S., & Wang, Y. (2019) · Chinese Medicine · doi:10.1186/s13020-019-0224-2 · Cited by 36
Williams, J. J. L., Alotaiq, N., Mullen, W., Burchmore, R., Liu, L., Baillie, G. S., Schaper, F., Pilch, P. F., & Palmer, T. M. (2018) · Nature Communications · doi:10.1038/s41467-017-02585-y · Cited by 35
“…SOCS3 can inhibit gp130 signalling independently of interaction with the SOCS3 binding site and works instead via direct inhibition of JAK1 19,56 These data would also suggest that any functional de fi cits in Δ PEST SOCS3 in localising to gp130 would be overcome by its overexpression.”
Self-citationRossa, C., Sommer, G., Spolidório, L. C., Rosenzweig, S. A., Watson, D. K., & Kirkwood, K. L. (2012) · PLoS ONE · doi:10.1371/journal.pone.0045197 · Cited by 35
“Because SOCS3-mediated suppression of gp130 receptor signaling is via association with the cytoplasmic portion of the receptor [13], a predominant nuclear localization would be expected to impair its function.”
van de Geijn, G. M., Gits, J., & Touw, I. P. (2004) · Journal of Leukocyte Biology · doi:10.1189/jlb.0104041 · Cited by 35
Competitive binding of STATs to receptor phospho-Tyr motifs accounts for altered cytokine responses
Wilmes, S., Jeffrey, P.-A., Martínez‐Fábregas, J., Hafer, M., Fyfe, P. K., Pöhler, E., Gaggero, S., López‐García, M., Lythe, G., Taylor, C., et al. (2021) · eLife · doi:10.7554/elife.66014 · Cited by 35
“Furthermore, negative feedback mechanisms, controlled by SOCSs and phosphatases, have been described as critical players influencing STAT1 and STAT3 phosphorylation kinetics and thereby shaping their signal integration for GP130-utilizing cytokines (Schmitz et al., 2000; Yasukawa et al., 2003; Croker et al., 2003; Bre…”
BackgroundEndothelial Progenitor Cells in the Host Defense Response
Shi, X., Seidle, K. A., Simms, K. J., Dong, F., Chilian, W. M., & Zhang, P. (2022) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2022.108315 · Cited by 37
Gu, Q., Kong, Y., Yu, Z., Li, B., & Xiao, Y. (2011) · Biochimie · doi:10.1016/j.biochi.2011.02.009 · Cited by 36
Croker, B. A., Mielke, L. A., Wormald, S., Metcalf, D., Kiu, H., Alexander, W. S., Hilton, D. J., & Roberts, A. W. (2008) · Experimental Hematology · doi:10.1016/j.exphem.2008.02.008 · Cited by 34
Woldman, I., Varinou, L., Ramsauer, K., Rapp, B., & Decker, T. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m105320200 · Cited by 37
Vlotides, G., Zitzmann, K., Stalla, G. K., & Auernhammer, C. J. (2004) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2004.04.002 · Cited by 33
“In addition, SOCS-3 directly associates with specific intracellular tyrosine residues of the activated gp130 receptor subunit, thus interfering with SHP2 activation [20].”
BackgroundSH2 Domain-Containing Protein-Tyrosine Phosphatases
Neel, B. G., Chan, G., & Dhanji, S. (2010) · Elsevier eBooks · doi:10.1016/b978-0-12-374145-5.00098-x · Cited by 34
Maier, E., Mittermeir, M., Ess, S., Neuper, T., Schmiedlechner, A., Duschl, A., & Horejs‐Hoeck, J. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.661306 · Cited by 31
Estrogen and progesterone regulate the IL-6 signal transduction pathway in antibody secreting cells
Canellada, A. M., Álvarez, I. R., Berod, L., & Gentile, T. (2008) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2008.06.009 · Cited by 33
Qing, M., Nimmesgern, A., Heinrich, P. C., Schumacher, K., Vázquez-Jiménez, J. F., Hess, J., von Bernuth, G., & Seghaye, M.-C. (2003) · Critical Care Medicine · doi:10.1097/01.ccm.0000098858.64868.9c · Cited by 32
“binding to phosphotyrosine residues on Jak kinases or cytokine receptors such as the signal transducing receptor subunit gp130 (27, 28).”
BackgroundSelf-citationZeng, B., Li, H., Liu, Y., Zhang, Z., Zhang, Y., & Yang, R. (2008) · Cancer Research · doi:10.1158/0008-5472.can-07-6792 · Cited by 32
Heeg, K. M., & Dalpke, A. H. (2003) · Vaccine · doi:10.1016/s0264-410x(03)00202-0 · Cited by 32
Torsoni, M. A., Carvalheira, J. B. C., Calegari, V. C., Bezerra, R. M. N., Saad, M., Gontijo, J. A. R., & Velloso, L. A. (2004) · Journal of Endocrinology · doi:10.1677/joe.0.1810117 · Cited by 32
“In IL-6 signaling, for example, SOCS-3 transcripts are detected as early as 30 min following IL-6 treatment of cultured cells (Schmitz et al. 2000).”
BackgroundInfluentialWierenga, A., Schuringa, J., Eggen, B. J. L., Kruijer, W., & Vellenga, E. (2002) · Leukemia · doi:10.1038/sj.leu.2402425 · Cited by 32
A completely foreign receptor can mediate an interferon‐γ‐like response
Strobl, B., Arulampalam, V., Is'harc, H., Newman, S. J., Schlaak, J. F., Watling, D., Costa‐Pereira, A. P., Schaper, F., Behrmann, I., Sheehan, K. C. F., et al. (2001) · The EMBO Journal · doi:10.1093/emboj/20.19.5431 · Cited by 32
Self-citationHutchins, A. P., Diez, D., & Miranda-Saavedra, D. (2013) · JAK-STAT · doi:10.4161/jkst.25097 · Cited by 31
Li, B., Yu, Z., Qian, G., Qian, P., Jiang, J., Wang, G., & Bai, C. (2005) · Respiratory Physiology & Neurobiology · doi:10.1016/j.resp.2005.07.001 · Cited by 31
The Shp-2 tyrosine phosphatase
Lai, L. A., Zhao, C., Zhang, E. E., & Feng, G. (2003) · Topics in current genetics · doi:10.1007/978-3-540-40035-6_14 · Cited by 31
Mahboubi, K., & Pober, J. S. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m107542200 · Cited by 31
Sobota, R. M., Müller, P. J., Heinrich, P. C., & Schaper, F. (2008) · Biochemical Journal · doi:10.1042/bj20071572 · Cited by 29
Self-citationAberrant neuronal activity-induced signaling and gene expression in a mouse model of RASopathy
Altmüller, F., Pothula, S., Annamneedi, A., Nakhaei‐Rad, S., Montenegro‐Venegas, C., Pina-Fernández, E., Marini, C., Santos, M., Schanze, D., Montag, D., et al. (2017) · PLoS Genetics · doi:10.1371/journal.pgen.1006684 · Cited by 30
Chen, Z., Wang, S., Erekosima, N., Li, Y., Hong, J., Qi, X., Merkel, P. A., Nagabhushanam, V., Choo, E. M., Katial, R. K., et al. (2013) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2013.06.035 · Cited by 31
Mechanism of attenuation of leptin signaling under chronic ligand stimulation
Knobelspies, H., Zeidler, J., Hekerman, P., Bamberg‐Lemper, S., & Becker, W. B. (2010) · BMC Biochemistry · doi:10.1186/1471-2091-11-2 · Cited by 31
“SOCS1 is structurally similar to SOCS3 and is generally thought to inhibit JAKs by direct binding to the activation loop of the kinase, independent of receptor-tyrosine motifs [33,34,38].”
The role of proteolysis in interleukin-11 signaling
Lokau, J., Kespohl, B., Kirschke, S., & Garbers, C. (2021) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2021.119135 · Cited by 35
SOCS3 negatively regulates LIF signaling in neural precursor cells
Emery, B., Merson, T. D., Snell, C., Young, K. M., Ernst, M., & Kilpatrick, T. J. (2006) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2006.01.005 · Cited by 29
The T Cell STAT Signaling Network Is Reprogrammed within Hours of Bacteremia via Secondary Signals
Hotson, A. N., Hardy, J. W., Hale, M. B., Contag, C. H., & Nolan, G. P. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0803666 · Cited by 28
“For example, SOCS3 is known to inhibit IL-6 signaling by binding pY759 of gp130 (33) and we found that SOCS3 transcript levels were increased in splenocytes of bacteremic mice compared with those of control mice.”
BackgroundSHPS-1/SIRP1alpha contributes to interleukin-6 signalling.
Sobota, R. M., Müller, P. J., Khouri, C., Ullrich, A., Poli, V., Noguchi, T., Heinrich, P., & Schaper, F. (2008) · Cellular Signalling · doi:10.1016/j.cellsig.2008.03.005 · Cited by 28
Self-citationBoyle, K., & Robb, L. G. (2007) · Journal of Reproductive Immunology · doi:10.1016/j.jri.2007.02.003 · Cited by 28
“SOCS3 interacts with gp130, a common cytokine receptor for interleukin (IL)-6, LIF and other members of the IL-6 family of cytokines, and the interaction site has been mapped to phosphotyrosine (pTyr) 757 (Nicholson et al., 2000; Schmitz et al., 2000).”
BackgroundKuźmicki, M., Telejko, B., Wawrusiewicz‐Kurylonek, N., Citko, A., Lipińska, D., Pliszka, J., Wilk, J., Kalejta, K., Lemancewicz, A., Grabiec, M., et al. (2012) · Gynecological Endocrinology · doi:10.3109/09513590.2012.683055 · Cited by 28
“The suppressor of cytokine signaling (SOCS) proteins are feedback inhibitors of signaling pathways induced by cytokines, hormones and growth factors [1,2] such as interleukin-6 (IL-6 [3,4]), insulin [5–8] and leptin [9].”
BackgroundStarr, R., Fuchsberger, M., Lau, L. S., Uldrich, A. P., Goradia, A., Willson, T. A., Verhagen, A. M., Alexander, W. S., & Smyth, M. J. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0901010 · Cited by 28
Oncogenic deletion mutants of gp130 signal from intracellular compartments
Schmidt‐Arras, D., Müller, M., Stevanovic, M., Horn, S., Schütt, A., Bergmann, J., Wilkens, R., Lickert, A., & Rose‐John, S. (2013) · Journal of Cell Science · doi:10.1242/jcs.130294 · Cited by 26
“It has been shown that SOCS3 is upregulated by STAT3 to negatively regulate JAK kinase activity and to compete with SHP-2 for binding to phosphorylated Tyr759 of gp130 (Heinrich et al., 2003).”
MethodHigashi, N., Kunimoto, H., Kaneko, S., Sasaki, T., Ishii, M., Kojima, H., & Nakajima, K. (2004) · Genes to Cells · doi:10.1111/j.1356-9597.2004.00715.x · Cited by 26
Cebo, C., Durier, V., Lagant, P., Maes, E., Florea, D., Lefebvre, T., Strecker, G., Vergoten, G., & Zanetta, J. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m106816200 · Cited by 26
Yang, X., Albrecht, U., Zakowski, V., Sobota, R. M., Häussinger, D., Heinrich, P. C., Ludwig, S., Bode, J. G., & Schaper, F. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m313072200 · Cited by 26
Self-citationFAILED INTERLEUKIN-6 SIGNAL TRANSDUCTION IN MURINE SEPSIS
Abcejo, A. S., Andrejko, K., Raj, N., & Deutschman, C. (2009) · Critical Care Medicine · doi:10.1097/ccm.0b013e31819dee81 · Cited by 21
“In addition, suppressors of cytokine signaling-3 bind to gp130 (as well as JAK-1) with high affinity (21) and specifically affect tyrosine phosphorylation (22, 23).”
BackgroundLarge Granular Lymphocytic Leukemia: From Immunopathogenesis to Treatment of Refractory Disease
Zawit, M., Bahaj, W., Gurnari, C., & Maciejewski, J. P. (2021) · Cancers · doi:10.3390/cancers13174418 · Cited by 25
“3 (SOCS3) gene responsible for this physiologic negative-feedback found to be disrupted in LGLL [61,63].”
BackgroundIL-6: A New Era for the Treatment of Autoimmune Inflammatory Diseases
Kishimoto, T., Kang, S., & Tanaka, T. (2015) · Springer eBooks · doi:10.1007/978-4-431-55651-0_11 · Cited by 24
Moßner, S., Kuchner, M., Modares, N. F., Knebel, B., Al‐Hasani, H., Floss, D. M., & Scheller, J. (2020) · Journal of Biological Chemistry · doi:10.1074/jbc.ra120.013927 · Cited by 24
“Ba/F3/gp130 cells are commonly used in cytokine research, because after activation of gp130 signaling by stimulation with, for example, Hyper-IL-6 (a fusion protein of IL-6 and the soluble IL-6R) (22), these cells proliferate following STAT3 and ERK activation (Fig.”
MethodDevelopmental control of cortico-cerebral astrogenesis
Mallamaci, A. (2013) · The International Journal of Developmental Biology · doi:10.1387/ijdb.130148am · Cited by 26
“The phosphorylation-dependent Shp2 tyrosine phosphatase also binds to the LifRb/gp130 phospho-tyrosine residues which interact with Socs3, upon cytokine stimulation (Schmitz et al., 2000).”
BackgroundZhang, W., Wang, L., Wang, Q., Luo, X. G., Fang, D., Chen, Y., Pan, X., Man, J., Xia, Q., Jin, B., et al. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.276832 · Cited by 23
Litherland, S. A., Xie, T. X., Grebe, K. M., Davoodi‐Semiromi, A., Elf, J. L., Belkin, N. S., Moldawer, L. L., & Clare-Salzler, M. J. (2005) · Journal of Autoimmunity · doi:10.1016/j.jaut.2005.02.001 · Cited by 21
“This interaction dephosphorylates and re-activates Jak 2 in response to IL-6 and possibly prolactin [29,30,33].”
BackgroundInfluentialJoint disease caused by defective gp130-mediated STAT signaling
Naka, T., & Kishimoto, T. (2002) · Arthritis Research & Therapy · doi:10.1186/ar400 · Cited by 22
“SOCS-3 can strongly inhibit IL-6 signaling by competing for the SHP-2-gp130 interaction site by binding to the SH2-domain-containing SHP-2-interaction site in gp130 [15, 16 ].”
Kakan, S. S., Edman, M. C., Yao, A., Okamoto, C. T., Nguyen, A. L., Hjelm, B. E., & Hamm‐Alvarez, S. F. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.833254 · Cited by 21
“SOCS3 downregulation may lead to enhanced activity of proinflammatory IL6 family cytokines through its reduced ability to interact with gp130 (56) to modulate IL6 signaling, also potentially contributing to SS pathogenesis.”
BackgroundJones, L. L., Alli, R., Li, B., & Geiger, T. L. (2016) · The Journal of Immunology · doi:10.4049/jimmunol.1402953 · Cited by 23
Rolvering, C., Zimmer, A. D., Kozar, I., Hermanns, H. M., Letellier, E., Vallar, L., Nazarov, P. V., Nicot, N., Ginolhac, A., Haan, S., et al. (2016) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2016.12.006 · Cited by 22
Self-citationBartoe, J. L., & Nathanson, N. (2002) · Brain Research. Molecular Brain Research · doi:10.1016/s0169-328x(02)00452-7 · Cited by 20
FAIRLIE, W. D., SOUZA, D. D., NICOLA, N. A., & BACA, M. (2003) · Biochemical Journal · doi:10.1042/bj20030104 · Cited by 20
Combined treatment with PPAR-γ agonists in pancreatic cancer: a glimmer of hope for cancer therapy?
Dicitore, A., Caraglia, M., Colao, A., Zappavigna, S., Mari, D., Hofland, L., Persani, L., & Vitale, G. (2013) · Current Cancer Drug Targets · doi:10.2174/1568009611313040008 · Cited by 21
“SOCS-3 binds phosphorylated gp130 and negatively regulates the subsequent STAT-3 activation [101, 102], inhibiting JAK2/STAT-3 signalling in pancreatic acinar cells [103].”
BackgroundClahsen, T., Lehmann, U., Stross, C., Hermanns, H., Volkmer‐Engert, R., Schneider-Mergener, J., Heinrich, P., & Schaper, F. (2005) · Cellular Signalling · doi:10.1016/j.cellsig.2004.09.016 · Cited by 20
Self-citationZeitvogel, J., Dalpke, A. H., Eiz‐Vesper, B., Kracht, M., Dittrich‐Breiholz, O., Werfel, T., & Wittmann, M. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.280370 · Cited by 19
“receptor chain and thus preventing JAK phosphorylation (11, 12).”
BackgroundLinard, C., Marquette, C., Clarençon, D., Galonnier, M., Mathieu, J., Pennequin, A., Benderitter, M., & Gourmelon, P. (2005) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2005.07.007 · Cited by 19
JAK-STAT signaling as an ARDS therapeutic target: Status and future trends
Zhang, Y., Gao, Z., Jiang, F., Yan, H., Yang, B., He, Q., Luo, P., Xu, Z., & Yang, X. (2022) · Biochemical Pharmacology · doi:10.1016/j.bcp.2022.115382 · Cited by 18
Interaction of SOCS3 with NonO attenuates IL-1β-dependent MUC8 gene expression
Song, K. S., Kim, K., Chung, K. C., Seol, J. H., & Yoon, J. (2008) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2008.10.084 · Cited by 18
Veluswamy, P., Wacker, M., Stavridis, D., Reichel, T., Schmidt, H., Scherner, M. P., Wippermann, J., & Michels, G. (2021) · Viruses · doi:10.3390/v13071346 · Cited by 18
Interleukin-6; pathogenesis and treatment of autoimmune inflammatory diseases
Tanaka, T., Narazaki, M., Masuda, K., & Kishimoto, T. (2013) · Inflammation and Regeneration · doi:10.2492/inflammregen.33.054 · Cited by 19
Mahboubi, K., Kirkiles-Smith, N. C., Karras, J., & Pober, J. S. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m211867200 · Cited by 18
Karki, P., Ke, Y., Zhang, C.-O., Li, Y., Tian, Y., Son, S., Yoshimura, A., Kaibuchi, K., Birukov, K. G., & Birukova, A. A. (2020) · Journal of Biological Chemistry · doi:10.1074/jbc.ra120.014232 · Cited by 18
“IL-6 is a proinflammatory cytokine with its major role in various inflammatory diseases (17); binding of SOCS3 to IL-6 receptor gp130 at Tyr757 represses IL-6-induced inflammation (16).”
BackgroundPrognostic significance of STAT3/phosphorylated-STAT3 in tumor: a meta-analysis of literatures.
Kong, H., Zhang, Q., Zeng, Y., Wang, H., Wu, M., Zheng, T., Zeng, Y., & Shi, H. (2015) · Europe PMC (PubMed Central) · Cited by 17
Miyawaki, A., Iizuka, Y., Sugino, H., & Watanabe, Y. (2019) · PLoS ONE · doi:10.1371/journal.pone.0211123 · Cited by 16
Luckey, M. A., Kim, T., Prakhar, P., Keller, H. R., Crossman, A., Choi, S., Love, P. E., Walsh, S. T. R., & Park, J. (2020) · European Journal of Immunology · doi:10.1002/eji.201948307 · Cited by 17
Schmok, E., Dar, M. A., Behrends, J., Erdmann, H., Rückerl, D., Endermann, T., Heitmann, L., Heßmann, M., Yoshimura, A., Rose‐John, S., et al. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.01537 · Cited by 16
“SOCS3 binds to the gp130 receptor chain and regulates downstream STAT3-mediated signaling events (26).”
BackgroundGenetically Disparate Fayoumi Chicken Lines Show Different Response to Avian Necrotic Enteritis
Kim, D. K., Lillehoj, H. S., Jang, S. I., Lee, S. H., Hong, Y. H., & Lamont, S. J. (2015) · The Journal of Poultry Science · doi:10.2141/jpsa.0140203 · Cited by 15
“including IL6, IL10, IL8, and interferon-gamma (IFN-γ) (Schmitz et al., 2000; Stevenson et al., 2004; Hokenson et al., 2013; Spence et al., 2013).”
BackgroundTranscriptional Regulation of Hypothalamic Corticotropin-Releasing Factor Gene
Kageyama, K., & Suda, T. (2010) · Vitamins and hormones · doi:10.1016/s0083-6729(10)82016-3 · Cited by 15
Reuben, J. S., Dinh, L., Lee, J., Stateson, J., Kamara, H., Xiang, L., & Opperman, L. A. (2011) · Oral Surgery Oral Medicine Oral Pathology Oral Radiology and Endodontology · doi:10.1016/j.tripleo.2010.09.068 · Cited by 16
“SOCS3 was shown to differentially modulate IL-6 and IL-10 signaling in both human and mouse macrophages.74,75 The absence of SOCS3 has been implicated in switching IL-6–induced proinflammatory responses to those more characteristic of the antiinflammatory cytokine IL-10.”
BackgroundInfluentialThe Vesicular Stomatitis Virus Matrix Protein Inhibits Glycoprotein 130-Dependent STAT Activation
Terstegen, L., Gatsios, P., Ludwig, S., Pleschka, S., Jahnen‐Dechent, W., Heinrich, P. C., & Graeve, L. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.167.9.5209 · Cited by 15
“activation required tyrosine 759 of the cytoplasmic domain of gp130, which upon phosphorylation might recruit SOCS-3 to the activated receptor complex (12, 13).”
BackgroundSelf-citationCaspase-mediated cleavage of the signal-transducing IL-6 receptor subunit gp130
Graf, D., Haselow, K., Münks, I., Bode, J. G., & Häussinger, D. (2008) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2008.06.009 · Cited by 14
Kuramoto, M., Kawashima, N., Tazawa, K., Nara, K., Fujii, M., Noda, S., Hashimoto, K., Nozaki, K., & Okiji, T. (2020) · International Endodontic Journal · doi:10.1111/iej.13386 · Cited by 14
Kageyama, K., Tamasawa, N., & Suda, T. (2011) · Stress · doi:10.3109/10253890.2010.536279 · Cited by 14
“IL-6 stimulates the Janus kinase/signal transducers and activators of the transcription (JAK/STAT) signaling pathway, while IL-6-induced SOCS-3 acts as a negative regulator and inhibits STAT phosphorylation by JAK at the receptor complex (Ram and Waxman 1999; Schmitz et al. 2000).”
BackgroundYoon, J.-I., Cho, H., Jeon, R., & Sung, M. (2022) · Pharmaceuticals · doi:10.3390/ph15121515 · Cited by 14
“Considering the fact that SOCS3 was negatively regulated by the complex of SH2 domain-containing protein-tyrosine phosphatases 2 and tyrosine 759 in gp130, which does not affect SOCS1, SOCS3 is assumed to act as a feedback regulator for inflammation [49].”
BackgroundWang, S., Zheng, G., Zhao, L., Xu, F., & Qian, J. (2015) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.12629 · Cited by 14
“Consequently, this mechanism leads to Stat3 activation [38, 39].”
BackgroundDoumanov, J. A., Daubrawa, M., Unden, H., & Graeve, L. (2005) · Cellular Signalling · doi:10.1016/j.cellsig.2005.09.006 · Cited by 14
Mechanism of crosstalk inhibition of IL-6 signaling in response to LPS and TNFα
Kiu, H., Hilton, D. J., Nicola, N. A., Ernst, M., Márquez, R., Alexander, W. S., Roberts, A. W., & McManus, E. J. (2007) · Growth Factors · doi:10.1080/08977190701830151 · Cited by 14
“Work in several laboratories has firmly established that both SOCS3 and SHP2 exert their negative effects on IL-6 signaling through binding to this residue once phosphorylated (Stahl et al. 1995; Nicholson et al. 2000; Schmitz et al. 2000; Lehmann et al. 2003).”
BackgroundPukos, N., Yoseph, R., & McTigue, D. M. (2018) · Neuroglia · doi:10.3390/neuroglia1010007 · Cited by 17
Metadata
- Authors
- Schmitz, J., Weissenbach, M., Haan, S., Heinrich, P. C., & Schaper, F.
- Affiliations
- RWTH Aachen University (DE)
- Corresponding author
- Heinrich, Peter C.
- ORCID
- Schaper, Fred
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2000-04
- Volume
- 275
- Issue
- 17
- Pages
- 12848-12856
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2038468714
- Cited by
- 388
- References
- 36
- Citations by year
- 2026: 4 · 2025: 1 · 2024: 4 · 2023: 3 · 2022: 9 · 2021: 10 · 2020: 10 · 2019: 7 · 2018: 8 · 2017: 14 · 2016: 10 · 2015: 10 · 2014: 13 · 2013: 10 · 2012: 23
- FWCI
- 15.16
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Open Repository and Bibliography (University of Luxembourg) (submittedVersion, cc-by-nc-sa)
- RWTH Publications (RWTH Aachen) (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Keywords
- SOCS3, IL-6 signaling, SHP2, gp130, suppressor of cytokine signaling, SOCS1, protein-protein interaction
- MeSH terms
- Suppressor of Cytokine Signaling 1 Protein, Suppressor of Cytokine Signaling 3 Protein, Interleukin-6 Inhibitors, alpha-Macroglobulins, Carrier Proteins, Cell Nucleus, Glutathione Transferase, Humans, Membrane Glycoproteins, Phosphorylation, Precipitin Tests, Promoter Regions, Genetic, Protein Binding, Proteins, Recombinant Fusion Proteins, Repressor Proteins, Transcription Factors, Transfection, Tumor Cells, Cultured, Tyrosine, Immunoblotting, Blotting, Northern, Signal Transduction, Antigens, CD, Interleukin-6, Protein Tyrosine Phosphatases, src Homology Domains, Intracellular Signaling Peptides and Proteins, Cytokine Receptor gp130, Suppressor of Cytokine Signaling Proteins, Protein Tyrosine Phosphatase, Non-Receptor Type 6, Protein Tyrosine Phosphatase, Non-Receptor Type 11, SH2 Domain-Containing Protein Tyrosine Phosphatases
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
