Activation of Fes Tyrosine Kinase by gp130, an Interleukin-6 Family Cytokine Signal Transducer, and Their Association

Matsuda, Tadashi; Fukada, Toshiyuki; Takahashi-Tezuka, Mariko; Okuyama, Yoshiki; Fujitani, Yoshio; Hanazono, Yutaka; Hirai, Hisamaru; Hirano, Toshio

doi:10.1074/jbc.270.19.11037

Cited by 120 publications

(51 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Activation of the SHP-2 phosphatase may further lead to downregulation of the signal (Kim et al, 1998;Symes et al, 1997). In addition, other molecules such as vav (Lee et al, 1997) or tyrosine kinases Hck (Ernst et al, 1994), Tec, Btk (Matsuda et al, 1995b) and Fes (Matsuda et al, 1995a) have been reported to become phosphorylated upon gp130 stimulation, but their contribution to signal transduction is unclear.…”

Section: Introductionmentioning

confidence: 99%

Interleukin-6 and oncostatin M-induced growth inhibition of human A375 melanoma cells is STAT-dependent and involves upregulation of the cyclin-dependent kinase inhibitor p27/Kip1

Heinrich²,

et al. 1999

Self Cite

View full text Add to dashboard Cite

Interleukin-6 (IL-6)-type cytokines lead to growth arrest of human A375 melanoma cells. The present study demonstrates that this e ect depends on the activation of STAT transcription factors. We observed a correlation between the extent of growth inhibition exerted by IL-6, IL-6 plus soluble IL-6 receptor or oncostatin M (OSM) and the intensities of STAT3 and STAT1 signals. A truncated chimeric receptor retaining only the membrane-proximal region of gp130, the common signal transducer of IL-6-type cytokines, did neither activate STATs nor mediate growth arrest of stable transfectants. These functions were restored by the addition of short STAT recruitment modules comprising critical tyrosine residues from gp130 (Y767, Y814). A receptor carrying tyrosine module Y759 of gp130 e ectively mediated activation of the phosphatase SHP-2 but did not alter cell growth. Overexpression of dominant negative forms of STAT3 but not STAT1 abrogated the inhibitory e ect of OSM and IL-6 in A375 cells. In addition, we have identi®ed the cyclin-dependent kinase inhibitor p27/Kip1 as a novel target to be regulated by IL-6-type cytokines. Stimulation-dependent upregulation of p27 mRNA occurred STAT3-dependently. Also p27 protein accumulated which coincided with the disappearance of hyperphosphorylated retinoblastoma protein in three human melanoma cell lines sensitive to IL-6-type cytokines.

show abstract

Section: Introductionmentioning

confidence: 99%

Interleukin-6 and oncostatin M-induced growth inhibition of human A375 melanoma cells is STAT-dependent and involves upregulation of the cyclin-dependent kinase inhibitor p27/Kip1

Heinrich²,

et al. 1999

Self Cite

View full text Add to dashboard Cite

show abstract

“…IL-6 induced Fer tyrosine phosphorylation within 5 minutes (Fig. 2C), suggesting the possibility that Fer could be involved with IL-6 receptor (gp130) similarly to its homologue Fes (28). Given the expression of gp130 in PC-3 cells (30), we investigated whether Fer may be involved early in IL-6 signaling (i.e., at the receptor level).…”

Section: Fer Is a Partner Of Il-6 Signaling Molecules In Prostate Canmentioning

confidence: 99%

“…Basically, IL-6 binds to its cognate a-chain receptor (IL-6 receptor) with low affinity, and then the complex binds to the signal-transducing molecule gp130 (h-subunit) to form a high-affinity complex (27). IL-6 induces rapid phosphorylation of gp130; this phosphorylation can be induced by JAKs or Fes tyrosine kinases and triggers the signaling cascade leading to STAT3 phosphorylation, dimerization and nuclear translocation, and action at the gene level (28,29). Because Fer interacts with STAT3 in PC-3 cells, we investigated if this complex is modulated by IL-6.…”

Section: Fer Is a Partner Of Il-6 Signaling Molecules In Prostate Canmentioning

confidence: 99%

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

“…17 JAKs are not the only kinases that are associated with signal transduction by gp130. Additional, cytoplasmic protein tyrosine kinases (PTK) are found in complex with gp130, which, depending on the cell type, include Src kinases, (Lyn, 18 c-Src, c-Yes, 19,20 Fyn, 21 and Hck 22 ), Fes, 23 and Tec. 24 Several of these kinases also participate in the signal transduction by other hematopoietin receptors and by protein tyrosine kinase receptors for growth factors including EGF.…”

mentioning

confidence: 99%

Modulation of hepatic acute phase gene expression by epidermal growth factor and src protein tyrosine kinases in murine and human hepatic cells

et al. 1999

View full text Add to dashboard Cite

Activation of Fes Tyrosine Kinase by gp130, an Interleukin-6 Family Cytokine Signal Transducer, and Their Association

Cited by 120 publications

References 36 publications

Interleukin-6 and oncostatin M-induced growth inhibition of human A375 melanoma cells is STAT-dependent and involves upregulation of the cyclin-dependent kinase inhibitor p27/Kip1

Interleukin-6 and oncostatin M-induced growth inhibition of human A375 melanoma cells is STAT-dependent and involves upregulation of the cyclin-dependent kinase inhibitor p27/Kip1

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

Modulation of hepatic acute phase gene expression by epidermal growth factor and src protein tyrosine kinases in murine and human hepatic cells

Contact Info

Product

Resources

About