Regulation of the trans-activation potential of STAT5 through its DNA-binding activity and interactions with heterologous transcription factors

Groner, Bernd; Fritsche, Michael; Stöcklin, Elisabeth; Berchtold, Susanne; Merkle, Christian; Moriggl, Richard; Pfitzner, Edith

doi:10.1016/s1096-6374(00)80004-0

Cited by 28 publications

(24 citation statements)

References 40 publications

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“…In the case of oestrogen receptor-α, direct interaction with STAT5, requiring the oestrogen receptor-α DNA-binding domain, has been reported [49]. Finally, in direct contrast with our findings using HNF4α, cross-talk between STAT5 and the glucocorticoid receptor that is synergistic towards STAT5 transcription but is inhibitory towards glucocorticoid receptor-dependent transcription has been described [26].…”

Section: Discussioncontrasting

confidence: 96%

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Signalling cross-talk between hepatocyte nuclear factor 4α and growth-hormone-activated STAT5b

Park

Wiwi

Waxman

2006

Biochemical Journal

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In the present study, we have characterized signalling cross-talk between STAT5b (signal transducer and activator of transcription 5b) and HNF4α (hepatocyte nuclear factor 4α), two major regulators of sex-dependent gene expression in the liver. In a HepG2 liver cell model, HNF4α strongly inhibited β-casein and ntcp (Na + /taurocholate cotransporting polypeptide) promoter activity stimulated by GH (growth hormone)-activated STAT5b, but had no effect on interferon-γ -stimulated STAT1 transcriptional activity. By contrast, STAT5b synergistically enhanced the transcriptional activity of HNF4α towards the ApoCIII (apolipoprotein CIII) promoter. The inhibitory effect of HNF4α on STAT5b transcription was associated with the inhibition of GH-stimulated STAT5b tyrosine phosphorylation and nuclear translocation. The short-chain fatty acid, butyrate, reversed STAT5b transcriptional inhibition by HNF4α, but did not reverse the inhibition of STAT5b tyrosine phosphorylation. HNF4α inhibition of STAT5b tyrosine phosphorylation was not reversed by pervanadate or by dominant-negative phosphotyrosine phosphatase 1B, suggesting that it does not result from an increase in STAT5b dephosphorylation. Rather, HNF4α blocked GHstimulated tyrosine phosphorylation of JAK2 (Janus kinase 2), a STAT5b tyrosine kinase. Thus STAT5b and HNF4α exhibit bidirectional cross-talk that may augment HNF4α-dependent gene transcription while inhibiting STAT5b transcriptional activity via the inhibitory effects of HNF4α on JAK2 phosphorylation, which leads to inhibition of STAT5b signalling initiated by the GH receptor at the cell surface.

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Section: Discussioncontrasting

confidence: 96%

“…Co-operative interaction between STAT5b and HNF4α leading to regulation of a female-specific CYP promoter has also been described [23]. Finally, both stimulatory and inhibitory cross-talk may occur between STAT5b and certain nuclear receptors [24][25][26].…”

Section: Introductionmentioning

confidence: 95%

Signalling cross-talk between hepatocyte nuclear factor 4α and growth-hormone-activated STAT5b

Park

Wiwi

Waxman

2006

Biochemical Journal

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“…However, Stat5 transcriptional activity in this context remains latent. Subsequent glucocorticoid stimulation does not affect Stat5 tyrosine phosphorylation but leads to the serine dephosphorylation of both Stat5 isoforms, which translates into an increase in Stat5 transcriptional activity (Groner et al, 2000). Conversely, Stat5a-dependent transcription of a GH-responsive ntcp-reporter gene positively depends on Ser731 of Stat5b and Ser780 of Stat5a (and not Ser726) (Park et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

“…Conversely, growth hormone (GH) stimulation of a GH-responsive luciferase reporter is positively dependent on Ser730 of Stat5b and Ser780 but not Ser726 of Stat5a (Yamashita et al, 2001). Finally, Stat5a/b transcriptional activity can be also regulated by interaction with other nuclear proteins (Grimley et al, 1999, Groner et al, 2000.…”

Section: Introductionmentioning

confidence: 99%

STAT5a Activation Mediates the Epithelial to Mesenchymal Transition Induced by Oncogenic RhoA.

Benitah¹,

Valerón²,

Rui

et al. 2003

MBoC

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The involvement of Rho GTPases in signal transduction pathways leading to transcription activation is one of the major roles of this family of GTPases. Thus, the identification of transcription factors regulated by Rho GTPases and the understanding of the mechanisms of their activation and its biological outcome are of great interest. Here, we provide evidence that Rho GTPases modulate Stat5a, a transcription factor of the family of signal transducers and activators of transcription. RhoA triggers tyrosine phosphorylation (Y696) of Stat5a via a JAK2-dependent mechanism and promotes DNA-binding activity of Stat5a. Tyrosine phosphorylation of Stat5a is also stimulated physiologically by lysophosphatidic acid (LPA) in a Rho-dependent manner. Simultaneously, RhoA reduces serine phosphorylation of Stat5a at both serine residues S726 and S780, resulting in a further increase of activity as defined by mutagenesis experiments. Furthermore, serine dephosphorylation of Stat5a by RhoA does not take place by down-modulation of either JNK1, MEK1, or p38 MAP kinases, as determined by transfection experiments or chemical inhibition of both MEK1, p38, and JNK serine kinases. Thus, RhoA regulates Stat5a via tyrosine phosphorylation and via a yet to be determined novel down-modulating pathway that involves serine dephosphorylation. Finally, we provide evidence for a role of Stat5a in RhoA-induced epithelial-to-mesenchymal transition with concomitant increase in vimentin expression, E-cadherin down-regulation, and cell motility

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“…In parental PC12 cells, the activation of Stat5b might be required for the initial burst of growth and subsequent NGF-dependent differentiation. In PC12/Tat cells the activation of Stat5a, by heterodimerizing with Stat5b, may counteract the positive effect of Stat5b on differentiation (Groner et al, 2000). Alternatively, in PC12/Tat cells Stat5a may utilize a Stat5b-independent pathway and directly target its downstream genes.…”

Section: Discussionmentioning

confidence: 99%

HIV-Tat promotes cellular proliferation and inhibits NGF-induced differentiation through mechanisms involving Id1 regulation

et al. 2004

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Regulation of the trans-activation potential of STAT5 through its DNA-binding activity and interactions with heterologous transcription factors

Cited by 28 publications

References 40 publications

Signalling cross-talk between hepatocyte nuclear factor 4α and growth-hormone-activated STAT5b

Signalling cross-talk between hepatocyte nuclear factor 4α and growth-hormone-activated STAT5b

STAT5a Activation Mediates the Epithelial to Mesenchymal Transition Induced by Oncogenic RhoA.

HIV-Tat promotes cellular proliferation and inhibits NGF-induced differentiation through mechanisms involving Id1 regulation

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