FER Kinase Activation of Stat3 Is Determined by the N-terminal Sequence

Priel-Halachmi, Smadar; Ben-Dor, Israel; Shpungin, Sally; Tennenbaum, Tamar; Molavani, Hana; Bachrach, Michal; Salzberg, Samuel; Nir, Uri

doi:10.1074/jbc.m003402200

Cited by 26 publications

(33 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Fer has been reported to interact with STAT3 in different cell systems (18,19,24). Because Fer and pSTAT3 seemed to be expressed in the same subcellular compartments in subsets of tumor cells of prostate cancer specimens ( Fig.…”

Section: Fer Forms Complexes With Stat3 In Prostate Cancer Cell Linesmentioning

confidence: 95%

“…It has been reported that overexpression of Fer in COS cells increases STAT3 tyrosine phosphorylation (18). We tested whether Fer activity may determine the status of STAT3 activation.…”

Section: Fer Phosphorylates Stat3mentioning

confidence: 99%

“…Based on Fer activation of STAT3 by Y705 phosphorylation (pSTAT3; ref. 18), phosphotyrosinespecific STAT3 antibodies were then used to investigate pSTAT3 staining along with Fer in prostate tissues. Figure 1B (right) shows weak pSTAT3 antibodies immunoreactivity in benign glands and a strong signal resembling that of Fer in both the cytoplasm and nucleus of prostate tumor cells.…”

Section: Fer and Pstat3 Expression And Colocalization In Human Prostamentioning

confidence: 99%

“…18) and with phosphatidylinositol 3-kinase in insulin signaling, thereby suggesting a role in cell survival (19). Furthermore, Fer dominant negative was shown to interfere with STAT3 phosphorylation in CHO and COS cells (18). This connection of Fer with STAT3 is particularly attractive in the context of prostate cancer.…”

Section: Introductionmentioning

confidence: 98%

“…Fer has been reported to interact with the signal transducer and activator of transcription 3 (STAT3; ref. 18) and with phosphatidylinositol 3-kinase in insulin signaling, thereby suggesting a role in cell survival (19). Furthermore, Fer dominant negative was shown to interfere with STAT3 phosphorylation in CHO and COS cells (18).…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

The Fer Tyrosine Kinase Cooperates with Interleukin-6 to Activate Signal Transducer and Activator of Transcription 3 and Promote Human Prostate Cancer Cell Growth

Zoubeidi

Rocha²,

Zouanat³

et al. 2009

Molecular Cancer Research

View full text Add to dashboard Cite

Androgen withdrawal is the most effective form of systemic therapy for men with advanced prostate cancer. Unfortunately, androgen-independent progression is inevitable, and the development of hormone-refractory disease and death occurs within 2 to 3 years in most men. The understanding of molecular mechanisms promoting the growth of androgenindependent prostate cancer cells is essential for the rational design of agents to treat advanced disease. We previously reported that Fer tyrosine kinase level correlates with the development of prostate cancer and aggressiveness of prostate cancer cell lines. Moreover, knocking down Fer expression interferes with prostate cancer cell growth in vitro. However, the mechanism by which Fer mediates prostate cancer progression remains elusive. We present here that Fer and phospho-Y705 signal transducer and activator of transcription 3 (STAT3) are barely detectable in human benign prostate tissues but constitutively expressed in the cytoplasm and nucleus of the same subsets of tumor cells in human prostate cancer. The interaction between STAT3 and Fer was observed in all prostate cancer cell lines tested, and this interaction is mediated via the Fer Src homology 2 domain and modulated by interleukin-6 (IL-6). Moreover, IL-6 triggered a rapid formation of Fer/gp130 and Fer/STAT3 complexes in a time-dependent manner and consistent with changes in Fer and STAT3 phosphorylation and cytoplasmic/nuclear distribution. The modulation of Fer expression/activation resulted in inhibitory or stimulatory effects on STAT3 phosphorylation, nuclear translocation, and transcriptional activation. These effects translated in IL-6 -mediated PC-3 cell growth. Taken together, these results support an important function of Fer in prostate

show abstract

Section: Fer Forms Complexes With Stat3 In Prostate Cancer Cell Linesmentioning

confidence: 95%

“…It has been reported that overexpression of Fer in COS cells increases STAT3 tyrosine phosphorylation (18). We tested whether Fer activity may determine the status of STAT3 activation.…”

Section: Fer Phosphorylates Stat3mentioning

confidence: 99%

Section: Fer and Pstat3 Expression And Colocalization In Human Prostamentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

The Fer Tyrosine Kinase Cooperates with Interleukin-6 to Activate Signal Transducer and Activator of Transcription 3 and Promote Human Prostate Cancer Cell Growth

Zoubeidi

Rocha²,

Zouanat³

et al. 2009

Molecular Cancer Research

View full text Add to dashboard Cite

show abstract

Hypertonic preconditioning prevents hepatocellular injury following ischemia/reperfusion in mice: A role for interleukin 10

Oreopoulos

Szaszi

et al. 2004

Hepatology

View full text Add to dashboard Cite

Ischemia/reperfusion (I/R) of the liver occurs in many clinical scenarios including trauma, elective surgery, and transplantation. Events initiated by this process can lead to inflammation in the liver, culminating in local injury as well as distant organ dysfunction. Recent studies have suggested that hypertonic saline exerts anti-inflammatory effects, which may be beneficial in preventing organ injury. In the present study, we examine the effect of hypertonic saline on the development of liver inflammation following I/R in both rat and mouse models. Hypertonic pretreatment was shown to prevent liver enzyme release concomitant with a reduction in liver neutrophil sequestration. Hypertonic saline appeared to exert this effect by inhibiting liver tumor necrosis factor ␣ (TNF-␣) generation, an effect that culminated in reduced liver adhesion molecule expression. Hypertonic saline pretreatment was shown to augment liver interleukin 10 (IL-10) expression following I/R, as a potential mechanism underlying its anti-inflammatory effect. To examine the role of IL-10 in the protective effect of hypertonic saline on liver I/R injury, we used a murine model of I/R. In wild type mice, hypertonic pretreatment similarly prevented liver injury induced by I/R. However, in IL-10 knockout animals, hypertonic pretreatment was unable to prevent the liver enzyme release, TNF-␣ generation, or neutrophil sequestration induced by I/R. In conclusion, these findings define a novel mechanism responsible for the anti-inflammatory effects of hypertonic saline and also suggest a potential clinical role for hyperosmolar solutions in the prevention of liver injury associated with I/R. Supplementary material for this article can be found on the HEPATOLOGY website (http://interscience.wiley.com/jpages/0270-9139/suppmat/index.html). (HEPATOLOGY 2004;40:211-220.)

show abstract

Fer kinase sustains the activation level of ERK1/2 and increases the production of VEGF in hypoxic cells

Salem

Shpungin

Pasder

et al. 2005

Cellular Signalling

View full text Add to dashboard Cite

FER Kinase Activation of Stat3 Is Determined by the N-terminal Sequence

Cited by 26 publications

References 44 publications

The Fer Tyrosine Kinase Cooperates with Interleukin-6 to Activate Signal Transducer and Activator of Transcription 3 and Promote Human Prostate Cancer Cell Growth

The Fer Tyrosine Kinase Cooperates with Interleukin-6 to Activate Signal Transducer and Activator of Transcription 3 and Promote Human Prostate Cancer Cell Growth

Hypertonic preconditioning prevents hepatocellular injury following ischemia/reperfusion in mice: A role for interleukin 10

Fer kinase sustains the activation level of ERK1/2 and increases the production of VEGF in hypoxic cells

Contact Info

Product

Resources

About