Suppressors of cytokine signaling (SOCS) 1 and SOCS3 interact with and modulate fibroblast growth factor receptor signaling

Ben-Zvi, Tal; Yayon, Avner; Gertler, Arieh; Monsonego-Ornan, Efrat

doi:10.1242/jcs.02740

Cited by 52 publications

(46 citation statements)

References 68 publications

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“…Furthermore, SOCS-3 can bind to tyrosine kinase receptors and interfere with their signal transduction. Ben-Zvi et al (2006) could show that SOCS-3 and SOCS-1 bind to FGFR3 in HEK-293T cells. In those cells, SOCS-1 overexpression elevated MAPK phosphorylation, in contrast to the effect of SOCS-3 in prostate cancer, and repressed STAT1 phosphorylation.…”

Section: Socs-3 Is a Regulator Of Receptor Tyrosine Kinasesmentioning

confidence: 96%

SOCS-3 antagonises the proliferative and migratory effects of fibroblast growth factor-2 in prostate cancer by inhibition of p44/p42 MAPK signalling

Puhr¹,

Santer²,

Neuwirt³

et al. 2010

Endocrine-Related Cancer

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Fibroblast growth factor-2 (FGF-2) is highly expressed in prostate cancer. It promotes tumour progression through multiple pathways including those of signal transducers and activators of transcription factor 3 (STAT3), mitogen-activated protein kinases (MAPKs) and Akt. In previous studies, we have reported that STAT3 phosphorylation inversely correlates with suppressor of cytokine signalling-3 (SOCS-3) expression in prostate cancer cells. Recently, it has become evident that SOCS-3-negative regulation is not only limited to the interleukin-6 (IL-6) receptor. We hypothesised that SOCS-3 interferes with FGF signalling, thus influencing the outcome of its action in prostate cancer cells. For this purpose, we treated DU-145 and LNCaP-IL-6C cells with increasing concentrations of FGF-2, and verified protein phosphorylation. In the presence of FGF-2, neither STAT3, STAT1, nor Akt could be phosphorylated. Solely the p44/p42 MAPK pathway was activated after FGF-2 stimulation. We show for the first time that SOCS-3 interferes with the FGF-2 signalling pathway by modulating p44 and p42 phosphorylation in prostate cancer cells. Decreased SOCS-3 protein expression results in increased MAPK phosphorylation, whereas SOCS-3 overexpression leads to a decreased cellular proliferation and migration. On the basis of the present results, we propose that SOCS-3 is a novel modulator of FGF-2-regulated cellular events in prostate cancer.

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Section: Socs-3 Is a Regulator Of Receptor Tyrosine Kinasesmentioning

confidence: 96%

SOCS-3 antagonises the proliferative and migratory effects of fibroblast growth factor-2 in prostate cancer by inhibition of p44/p42 MAPK signalling

Puhr¹,

Santer²,

Neuwirt³

et al. 2010

Endocrine-Related Cancer

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“…Similar to INSR, EGFR induces tyrosine phosphorylation of SOCS3 [58]. Another RTK, FGFR3 was found to be constitutively associated with SOCS3 independent of FGF stimulation or the receptor's kinase activity [36,57]. Thus it is most likely that SOCS3 associates with the RTKs and regulates downstream signaling by ubiquitination-dependent degradation of receptor.…”

Section: Socs3mentioning

confidence: 98%

“…Thus, it is suggested that SOCS1 association with FGFR3 and EGFR has similar regulatory functions as other RTKs. On the other hand, SOCS1 cooperated with FGFR3 to promote FGF induced MAPK phosphorylation through a still undefined mechanism [36]. A possible explanation is that SOCS proteins may not only act as ubiquitin ligases but also as adapters.…”

Section: Socs1mentioning

confidence: 99%

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SOCS proteins in regulation of receptor tyrosine kinase signaling

Kazi

Kabir

Flores‐Morales

2014

Cell. Mol. Life Sci.

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SOCS proteins in regulation of receptor tyrosine kinase signaling.Uddin, Kazi; Kabir, Nuzhat N; Flores-Morales, Amilcar; Rönnstrand, Lars Link to publication Citation for published version (APA): Kazi, J. U., Kabir, N. N., Flores-Morales, A., & Rönnstrand, L. (2014). SOCS proteins in regulation of receptor tyrosine kinase signaling. Cellular and Molecular Life Sciences, 71(17), 3297-3310. DOI: 10.1007/s00018-014-1619-y General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.• Users may download and print one copy of any publication from the public portal for the purpose of private study or research.• You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal Take down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. AbstractThe receptor tyrosine kinases (RTKs) are a family of cell surface receptors that play critical roles in signal transduction from extracellular stimuli. Many of this family of kinases are overexpressed or mutated in human malignancies and thus became attractive drug target for cancer treatment. The signaling mediated by RTKs must be tightly regulated by interacting proteins including protein-tyrosine phosphatases and ubiquitin ligases. The suppressor of cytokine signaling (SOCS) family proteins are well known negative regulators of cytokine receptors signaling consisting of eight structurally similar proteins, SOCS1-7 and CIS. A key feature of this family of proteins is the presence of an SH2 domain and a SOCS box. Recent studies suggest that SOCS proteins also play a role in RTK signaling. Activation of RTK results in transcriptional activation of SOCS encoding genes. These proteins associate with RTKs through their SH2 domains and subsequently recruit the E3 ubiquitin machinery through the SOCS box, and thereby limit receptor stability by inducing ubiquitination. In a similar fashion SOCS proteins negatively regulate mitogenic signaling by RTKs. It is also evident that RTKs sometimes can bypass SOCS regulation and SOCS proteins can even potentiate RTKs-mediated mitogenic signaling. Thus apart from negative regulation of receptor signaling, SOCS proteins may also influence signaling in other ways.

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“…For example, SOCS1is involved in the regulation of several receptors including platelet-derived growth factor receptor (PDGFR), colony-stimulating factor 1 receptor (CSF1R), FMS-like tyrosine kinase 3 (FLT3), stem cell factor (SCF) receptor (KIT), insulin receptor (INSR), proto-oncogene MET and AXL [8][9][10][11][12][13][14]. Similar regulatory roles were described for SOCS2, SOCS3 and SOCS6 as well [1].…”

Section: Socs Family Proteinsmentioning

confidence: 99%

SOCS6 is a selective suppressor of receptor tyrosine kinase signaling

2014

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General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.• Users may download and print one copy of any publication from the public portal for the purpose of private study or research.• You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal AbstractThe suppressors of cytokine signaling (SOCS) are well known negative regulators of cytokine receptor signaling. SOCS6 is one of eight members of the SOCS family of proteins. Similar to other SOCS proteins, SOCS6 consists of an uncharacterized extended N-terminal region followed by an SH2 domain and a SOCS box. Unlike other SOCS proteins, SOCS6 is mainly involved in negative regulation of receptor tyrosine kinase signaling. SOCS6 is widely expressed in many tissues and is found to be downregulated in many cancers including colorectal cancer, gastric cancer, lung cancer, ovarian cancer, stomach cancer, thyroid cancer, hepatocellular carcinoma and pancreatic cancer. SOCS6 is involved in negative regulation of receptor signaling by increasing degradation mediated by ubiquitination of receptors or substrate proteins and induces apoptosis by targeting mitochondrial proteins. Therefore, SOCS6 turns out as an important regulator of survival signaling and its activity is required for controlling receptor tyrosine kinase signaling.

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Suppressors of cytokine signaling (SOCS) 1 and SOCS3 interact with and modulate fibroblast growth factor receptor signaling

Cited by 52 publications

References 68 publications

SOCS-3 antagonises the proliferative and migratory effects of fibroblast growth factor-2 in prostate cancer by inhibition of p44/p42 MAPK signalling

SOCS-3 antagonises the proliferative and migratory effects of fibroblast growth factor-2 in prostate cancer by inhibition of p44/p42 MAPK signalling

SOCS proteins in regulation of receptor tyrosine kinase signaling

SOCS6 is a selective suppressor of receptor tyrosine kinase signaling

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